Necrotizing+fasciitis

=__**Disease/Drug of interest** : __=

**Motivation and Background** :
Necrotizing Fasciitis, often referred to as “flesh-eating disease” is an extremely rare, serious bacterial disease that spreads rapidly and ultimately leads to deterioration of the body’s infected soft tissue [6]. Symptoms of this particular disease include severe pain, fever, vomiting, as well as red and purple skin present in the affected area. In most cases, necrotizing fasciitis enters the body through burns, cuts, or any other type of break in a victim’s skin [2].The spread of the disease from person to person is not common. Rather, Necrotizing Fasciitis arises through openings in the skin, as aforementioned. Necrotizing Fasciitis can lead to such extensive loss of skin tissue that, if left untreated, can result in limb amputation and ultimately even death. This rare disease affects males and females equally, with roughly 600 to 700 cases diagnosed in the United States each year. Ultimately, 25%-30% of cases result in the death of the patient [4]. While a rare disease, Necrotizing Fasciitis affects its victims detrimentally. Without strict, early treatment of antibiotics and surgery, the patient may lose limbs and other extremities due to bacterial exposure.

(Figure 1) Graphic shows main modes of infection, risk factors, and some treatments associated with necrotizing fasciitis.

**[1]** ClinicalTrials.gov https://clinicaltrials.gov/ct2/results?term=penicillin%2Bg&Search=Search (accessed Feb 3, 2017). **[2]** National Institutes of Health https://rarediseases.info.nih.gov/diseases/6454/necrotizing-fasciitis (accessed Feb 4, 2017). **[3]** Class Schedule for Class 540 ORGANIC COMPOUNDS -- PART OF THE CLASS 532-570 SERIES https://www.uspto.gov/web/patents/classification/uspc540/sched540.htm (accessed Feb 4, 2017). **[4]** Necrotizing Fasciitis (Flesh-Eating Bacteria): Causes, Symptoms, and Treatment http://www.webmd.com/skin-problems-and-treatments/necrotizing-fasciitis-flesh-eating-bacteria#1 (accessed Feb 3, 2017). **[5]** Necrotizing Fasciitis (Soft Tissue Inflammation) http://www.healthline.com/health/necrotizing-soft-tissue-infection#Prevention8 (accessed Feb 3, 2017). **[6]** Necrotizing Fasciitis: A Rare Disease, Especially for the Healthy https://www.cdc.gov/features/necrotizingfasciitis/index.html (accessed Feb 4, 2017). **[7]** penicillin g | C16H18N2O4S - PubChem https://pubchem.ncbi.nlm.nih.gov/compound/5904#section=Top (accessed Feb 2, 2017). **[8]** Pfizerpen (Penicillin G potassium) Drug Information: Side Effects and Drug Interactions - Prescribing Information at RxList http://www.rxlist.com/pfizerpen-drug/side-effects-interactions.htm (accessed Feb 5, 2017). **[9]** The Editors of Encyclopedia Britannica. penicillin https://www.britannica.com/science/penicillin (accessed Feb 1, 2017). **[10]** Vollmer, W.; Bertsche, U. Biochimica et Biophysica Acta (BBA) - Biomembranes 2008, 1778 (9), 1714–1734. **[11]** Work, E. Journal of General Microbiology 1961, 25 (2), 167–189.
 * References: **

**External links:**
https://rarediseases.info.nih.gov/diseases/6454/necrotizing-fasciitis https://pubchem.ncbi.nlm.nih.gov/compound/5904#section=Top http://www.healthline.com/health/necrotizing-soft-tissue-infection#Prevention8

https://www.cdc.gov/features/necrotizingfasciitis/index.html

https://www.uspto.gov/web/patents/classification/uspc540/sched540.htm

=__**Target Information** : __= Eliminating necrotizing fasciitis is most efficiently accomplished through breaking down periplasmic murein (peptidoglycan) sacculus present within the bacterial cell wall [10]. Said mucopeptides (another term for peptidoglycans) are made up of linear chains of alternating amino sugars, mainly N-acetylglucosamine and N-acetylmuramic acid. Short peptide chains of roughly three to five amino acids in length are present as well, and its three dimensional, mesh-like structure forms from cross-links between said peptide chains. These cross links are catalyzed by the bacterial enzyme transpeptidase. If said enzyme is inhibited, the production of cell walls in bacteria halts, blocking the reproduction of group A Strep.



(Figure 2) Pictured above is the typical structure of the target with its associated binding region for Penicillin G attachment

** Size ** : molecular weight of the protein
1010.018 g/mol

** Location ** :
This particular target's location is in the peptidoglycan found within the cell walls of Group A Streptococcal bacteria. Drug binds and inhibits transpeptidase (target).

** Function in a normal cell ** :
Transpeptidase (the target) cross links the peptidoglycan found within bacterial cell walls, which ultimately leads to their functional structure and maintained stability.

__**Drug Information**** : **__ Penicillin G binds to D-alanyl-D-alanine carboxypeptidase /transpeptidase enzymes of the mucopeptides and inhibits their growth, preventing the further replication and spread of the bacterial strain throughout the body [11]. The antibiotic works effectively throughout all races and genders. Necrotizing Fasciitis is a terrible disease that, while rare, has a massive impact upon its victims. For the time being, Penicillin G is vital and efficient in the inhibition of transpeptidase enzymes present in bacterial cell walls. With this being said, advancements in technique and application however are needed to truly eradicate Necrotizing Fasciitis once and for all.

(figure 3) Structure of Penicillin G
 * Schematic figure of drug ** :

C 16 H 18 N 2 O 4 S [7]
 * Formula ** :

334.39 g/mol [7]
 * Molecular weight ** :

61-33-6 [7]
 * CAS Number ** :

Penicillin G is an antibiotic that is rapidly and readily absorbed by the body through both subcutaneous as well as intramuscular injections
 * Delivery method ** :

Penicillin G is generally harmless to the patient. In severe cases, however, patients that are given high doses of intravenous treatment are susceptible to potassium poisoning, cardiac arrest, congestive heart failure and coma [8].
 * Side effects ** :

Penicillin g; Benzylpenicillin; Benzylpenicillinic acid; Pfizerpen; Pencillin G; Benzylpenicillin G
 * Other names ** :

Pfizer.
 * Maker or company ** :

Due to its widespread use, Penicillin G does in fact have a patent in class 540, subclass 1 under organic compounds [3]
 * Is it patented ** ?

The antibiotic itself has also been extensively tested, with roughly 63 studies to date [1]
 * Clinical Trials Info ** :

__** Origin ** : __ Arose from original studies done by Scottish bacteriologist Alexander Fleming in the late 1920’s. Upon returning home from vacation, Fleming checked the petri dishes he left behind and to his surprise, discovered that colonies of streptococcal and staphylococcal bacteria did not survive in the presence of accidental contamination by the green mold Penicillium [9]. Fleming then isolated the mold, reproduced it through a liquid medium, and successfully created a cure for many bacterial infections, including group A Streptococcus.

Different combinations of other intravenous antibiotics are also extensively used, which include vancomycin, clindamycin, and piperacillin/tazobactam.
 * Alternatives to this drug ** :


 * Miscellaneous ** :

Necrotizing Fasciitis is not caused simply by one form of bacteria. In 55%-80% of cases, the disease is a result of a combination of different bacteria including group A Streptococcus, Escherichia coli, Clostridium, Klebsiella, Aeromonas hydrophila, and Staphylococcus aureus [5]. Streptococcus A, however, is the most prevalent form of bacteria found in the majority of cases, and Penicillin G is efficient in inhibiting said other forms as well.


 * Other uses ** : can this drug be used to treat other diseases/conditions?

Penicillin G is widely used to treat many other forms of bacterial infection including gonorrhea and syphilis, respectively. This is due to the fact that most bacteria share similar cell walls which contain peptidoglycan, and penicillin G inhibits the enzyme (transpeptidase) that constructs said cell walls.