User:CaldDalA/sandbox

Article Evaluation

The Royal Society page seems well balanced in its presentation of viewpoints, supported by the "good article" indicator on the top right. Of note on the talk page are major edits that significantly expanded the article, conversations about the relatedness of some material, discrepancies, and more recently the addition of official portraits as allowed by the Royal Society. The useful resources links worked and some redirected to the Royal Society itself.

The Wikipedia page for Robert Boyle has many citations, at least five of which were verified as functional. There are many quoted parts in the article; I'm not entirely sure when a cited and identified quote is plagiarism and when it's not. The Important Works section is well organized; listing by years makes it clear to sort through the information.

Potential Topics

Thermocycler: Thermal cycler

Edit to include more up to date visuals, industial uses, use in research

Cefoxitin: Cefoxitin considered stub

Can add how it works, susceptible and resistant bacteria, side effects

Possibly also Mueller-Hinton agar (stub), McFarland standards (requires citations/warning banner, stub) and Agar diffusion test (warning banner needs citations)

I am assigning myself cefoxitin because it considered a stub and has little information on the wikipedia page but a lot of information is available in general. Its interactions with other major drug types, the mechanism of affected proteins/structures and tests for susceptibility are all possible additions.

Potential sources:

http://www.antimicrobe.org/drugpopup/cefoxitin.htm

https://www.drugs.com/pro/cefoxitin.html

https://pubchem.ncbi.nlm.nih.gov/compound/cefoxitin#section=Related-Records

Cefoxitin

Uses in Medicine

Cornea. 2015 Jun;34(6):698-703. doi: 10.1097/ICO.0000000000000431.

Int J Surg. 2014 Dec;12(12):1300-5. doi: 10.1016/j.ijsu.2014.10.029. Epub 2014 Oct 31.

https://www.ncbi.nlm.nih.gov/pubmedhealth/?term=%28+%22Cefoxitin%22+%29

Morbidity and mortality weekly report : MMWR / Center ... v.32:no.45 (1983). https://hdl.handle.net/2027/umn.31951d00676007z

Medical bulletin. v.37 no.2 1980. https://hdl.handle.net/2027/mdp.39015072847828

When used in third and fourth degree perineum injuries in women after giving vaginal birth, cefoxitin decreases infection rate at two and six weeks.

The earlier and more times a child is exposed to cefoxitin, as with early and mutliple exposure to many antibiotics, the greater the likelihood of developing inflammatory bowel disease later in life. This may be due in part to a decreased variety of microorganisms in the digestive system.

Cefoxitin is used to treat pelvic inflammatory disease because it is a broad spectrum antibiotic. For outpatient treatment, oral antibiotics or those with more spread out doses may be prescribed.

It is also used to treat gonorrhea in both men and women with mild if any side effects. Cefoxitin is an effective alternative to peniciilin, methicillin and spectinomycin.

Mefoxin is sold in three major IV doses, 1g, 2g, and 10g. It is usually given every six to eight hours in 1g or 2g doses.

Taking Mefoxin may interfere with tests looking for urine glucose and result in a false positive. As with any antibiotic, do not take if allergic.

Cefoxitin is used to treat:

• Skin infections, primarily due to Staphylococcus
• Urinary tract infections
• Bronchitis
• Tonsilitis
• Ear infections
• Bacterial pneumonia
• May be given prior to surgery as a preventative measure
• E. coli caused infections
• Sepsis
• Bone and joint infections
• Abdominal infections and abscesses
• Perineum injuries
• Pelvic inflammatory disease
• Gonorrhea
• Infections of susceptible bacteria listed below

Bacterial Susceptibility

In a 2009 study, Funsun et al. found cefoxitin disk assays to correctly identify all 60 mecA-positive Staphyloccocus aureus, or MRSA isolates, to be resistant to cefoxitin.

Likewise, Fernandes et al in 2005 determined cefoxitin serves as an appropriate replacement for methicillin in determining if a bacteria displays methicillin resistance.

Literature values for determining susceptibility to cefoxitin via disk diffusions, also called Kirby Bauer disk diffussion, are greater than or equal to 22mm resulting in a "susceptible" result for S. aureus and greater than or equal to 25mm for coagulase-negative staphloccoci to be considered susceptible.

Major bacterial strains susceptible to cefoxitin include:

• mecA negative Staphyloccocus aureus
• Staphyloccus epidermis
• Streptococci strains
• E. coli
• Salmonellae
• P. vulgaris
• Flavobacter sp.
• Klebsiella sp.

Major bacteria resistant to cefoxitin:

• MRSA
• Enterococci
• Listeria monocytogenes
• Enterobacter sp.
• Bacteroides sp.

Mechanism--Separate from Microbiology

As a beta-lactamase inducer, cefoxitin is a beta-lactam antiobiotic, which binds penicillin binding proteins, or PBPs. In the presence of cefoxitin, bacteria that express beta lactamase will increase production and sercretion in an attempt to cleave the beta lactam ring. This production of beta-lactamase by Gram negative bacilli serves as a protective, or defensive mechanism against beta-lactam antibiotics. As a cephamycin, cefoxitin is highly resistant to hydrolysis or breakdown by beta-lactamase, in part due to the presence of the 7-alpha-methoxy functional group (see skeletal formula above).

Diets high in fat increase absorption of cefoxitin, particularly when paired with sodium salts, because lipids and fatty acid chains increase the intestinal wall's permeability to hydrophilic drugs. When taken with food, absorption rate increases by 15%.

Side Effects

Side effects for cefoxitin are regarded as mild. Common side effects include:

• local tenderness or pain at the site of injection

• skin color change, mild diahrrea

• mild nausea
• headache
• loss of appetite
• vaginal discharge and itching

• swelling of feet or legs.

While cefoxitin has not been associated with alcohol incompatibility like other members of the second generation cephalosporins class, it has been with a higher risk of coagulopathy, a bleeding disorder.

If any of the previous side effects are severe, or if an allergic reaction takes place immediately contact your doctor.

Notable Drug Interactions

Contraindications:

A contraindication means that the drug in question should not be used under particular circumstances. For cefoxitin, this includes patients who are hypersensitive to cephalosporin antibiotics.

Patients with colitis, kidney disease, or liver disease are also advised not to take cefoxitin. However, some drug databases will considers the diseases means for caution rather than contraindications.

Major or Severe:

Aside from the above mentioned contraindications and diseases which require monitoring by a doctor, the live cholera and live typhoid vaccines are known to have a severe interaction with cefoxitin.

Individuals on a low sodium diet, undergoing dialysis, or who have experienced seizures, particularly following antibiotic therapy, should also consult their physician prior to taking cefoxitin.

Moderate:

Only take additional antibiotics, anticoagulants and blood thinners under doctor supervision. Cefoxitin may decrease the effectiveness of hormonal birth control. This increases the risk for pregnancy and a medical consult will help determine whether backup birth control methods should be used.

Minor:

Minor drug interactions do not usually require a change in treatment. Your doctor may monitor specific events, such as bleeding, while taking cefoxitin. Two such minor interactions occur between cefoxitin and heparin as well as genistein.

PK/PD Data

Pharmocokinetic (PK) and pharmacodynamic (PD) data for cefoxitin are, as of 2013, considered limited and outdated. A few relatively recent studies have attempted to remedy that. One such study was by the Hôpitaux de Paris in collaboration with the french Ministry of Health. However, while the clinical trials were completed in 2015, no study data have been published. It should be noted that the expected results from using cefoxitin over carbapenems, another type of antibiotic with a wider bacterial spectrum, included effective treatment of E. coli produce extended spectrum beta-lactamase, less selective pressure on the GI tract which better maintains balanced flora, and a lower treatment cost. This followed a 2012 French study on the same E. coli strain with CTX-M-15 extended release beta-lactamase. Lepeule et. al. determined that in mice, the ideal pharmacodynamic target of fT>MIC=33%, where MIC is the minimum inhibitory concentration, was obtained with 200mg/kg every four hours. The fT>MIC (%) was increased by 11% when the administration frequency was increased from every four hours to every three hours. This implied that increasing the frequency might yield similar results in humans. The study also found no significant difference between the effectiveness of carbapenems and cefoxitin and suggested that cefoxitin can be used as an alternative treatment for CTX-M producing E. coli to carbapenems such as imipenem and ertapenem.

History of Cefoxitin

Groups of doctors at Merck, particularly Eli Lilly and his group-who also discovered erithromycin-discovered Cephamycin C while looking at penicillin producing bacteria. Cephamycin C was the first cephem discovered but while it was highly resistant to a lot of beta-lactamases-as is its derivative cefoxitin-it was almost only effective against Gram negative bacteria. The scientists used chemistry to modify the compound, which gives cefoxitin the title of semi-synthetic since a biological product is altered to artificially synthesize it. This new modification broadened its spectrum to include Gram positive bacteria. More than 300 modifications were made to the cephalosporin base with methoxy groups at the 7-alpha position, and yet cefoxitin was the compound that was successful in keeping its previous effectiveness against Gram negative bacteria, developed effectiveness against Gram positive bacteria, and was resistant to breakdown by beta-lactamase.

Cefoxitin, and the cephamycin family as a whole, served as a branching point and impulsed the discovery of more classes of beta-lactams. This is in part due to their primary discovery in the broths studied.

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References