Meningitis+Sp14

__**Disease/Drug of Interest: **__ **Bacterial meningitis/ceftriaxone ** __**Motivation and Background: **__

Meningitis is a serious condition caused by inflammation of the meninges, which are the membranes surrounding the brain. If not treated immediately, it can lead to death or severe complications such as brain damage, hearing loss, and learning disabilities [1]. Some of the symptoms of meningitis include stiff neck, severe headache, sensitivity to light, nausea, vomiting, and fever [2]. Bacterial meningitis can affect people of all ages, however young children have a higher risk of getting the disease. Bacterial meningitis is caused by several different bacteria, including //Haemophilus influenzae, Streptococcus pneumoniae, group B Streptococcus, Listeria monocytogenes//, and //Neisseria meningitides// [1]. These are all fairly common bacteria and many people are carriers, but they do not cause meningitis in most people. In order for the bacteria to infect the meninges, they must enter the central nervous system through the blood stream [3]. The bacteria can be exchanged through respiratory and throat conditions, and people living in close contact with someone who has the disease have an increased risk of catching it themselves. Bacterial meningitis infects people throughout the world, but certain areas of sub-Saharan Africa experience epidemics of meningitis [4]. This occurs because of the living conditions and lack of healthcare in these regions. Bacterial meningitis is a disease that must be taken seriously and treated with the proper medications in order to ensure the survival and health of the patient.



__**Target Information: **__

The target of the drug ceftriaxone is Penicillin-binding protein 2B (molecular weight 73872.3g/mol). The Penicillin-binding protein 2B is found in the cell membrane of the bacterial cells causing the infection. These penicillin binding proteins are common components of most bacterial cells. Penicillin-binding protein 2B is essential for cell wall biogenesis. It is an effective target because a bacterial cell will not survive without its cell wall. Preventing this protein from functioning properly will eventually casue the cell to burst and die.



__**Drug Information: **__

Although many antibiotics can be used to treat bacterial meningitis, ceftriaxone is a particularly effective option. The World Health Organization recommends it be used to treat epidemics of bacterial meningitis in places such as Africa, because just a single dose can be effective in treating the disease [4]. Ceftriaxone belongs to a family of antibiotics called third generation cephalosporins. In 1945 the first cephalosporin compounds were isolated from the fungus //Acremonium chrysogenum//,which was found in sewer water [5]. Since their discovery, there have been four generations of cephalosporins. Ceftriaxone is part of the third generation. This family of drugs is structurally related to penicillin and acts in a similar way against bacteria. Ceftriaxone binds to its target and inhibits its function. The targets of ceftriaxone are the penicillin binding proteins, which are essential to the formation of the cell wall [5]. Without the protection of the cell wall, the bacteria will burst and die. Ceftriaxone is a choice drug for the treatment of bacterial meningitis because it is effective against a broad range of bacteria, including the common causes of bacterial meningitis. Another factor to consider when selecting an antibiotic is antibiotic resistance. Many strains of meningitis-causing //H. inﬂuenzae// and //S. pneumonia// are developing resistance to the antibiotics ampicillin and chloramphenicol, which suggests that third generation cephalosporins such as ceftriaxone may be the best choice for treating bacterial meningitis [6]. Ceftriaxone can also be used to treat many other bacterial infections such as gonorrhea, pelvic inflammatory disease, and Lyme disease [7].



The chemical formula of ceftiaxone is C18H18N8O7S3 and it has a molecular weight of 554.58 g/mol. The CAS number is 73384-59 5. Ceftriaxone is injected either intravenously or intramuscularly. It can be given as a single dose, or daily for 4 to 14 days [7]. Common side effects are pain or tenderness of the injection site, headache, dizziness, sweating, flushing, and diarrhea. Some other, more severe, side effects include rash, bloody or watery stools, fever, stomach cramps, stomach pain or bloating, nausea, vomiting, heartburn, and chest pain [7]. Ceftriaxone is known by other names such as Biotrakson, Cefatriaxone, Rocephine, Ceftriazone, Rocephin, Ceftriaxona, and Ceftriaxonum. Many companies prodeuce generic ceftriaxone, and there are four patents related to the production of ceftriaxone in the U.S. according to the United States Patent and Trademark Office website. The clinicaltrials.gov website shows that there two drug trials testing the effects of ceftriaxone on patients with bacterial meningitis have been conducted recently.

There are many other antibiotics that can be used to treat bacterial meningitis. The drug administered to a patient will depend on the type of bacteria causing their meningitis. Some common alternatives include penicillin, chloramphenicol, vancomycin, and other 3rd generation cephalosporins such as cefotaxime.

__**References: **__

1. Centers for Disease Control and Prevention. Bacterial meningitis. [|http://www.cdc.gov/meningitis /bacterial.html]. (accessed February 3, 2014). 2. U.S. National Library of Medicine. Meningitis. [|http://www.nlm.nih.gov/medlineplus/ency/article /000680.htm]. (accessed February 3, 2014). 3. Hoffman, O.; Weber, R. J., Pathophysiology and treatment of bacterial meningitis. //Ther Adv Neurol Disord// **2009**, 2 (6), 1-7. 4. World Health Organization. Meningococcal meningitis. [|http://www.who.int/mediacentre/factsheets /fs141/en/index.html]. (accessed February 3, 2014). <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">5. Powers, J. H.. U.S. Food and Drug Administration. Use and importance of cephalosporins in human medicine. [] <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">/VeterinaryMedicineAdvisoryCommittee/ucm129875.htm. (accessed February 3, 2014). <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">6. Prasad, K.; Kumar, A.; Gupta, P. K.; Singhal, T., Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis. //Cochrane Database Syst Rev// **2007**, (4), CD001832. <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">7. U.S. National Library of Medicine. Ceftriaxone injection. [|http://www.nlm.nih.gov/medlineplus /druginfo/meds/a685032.html]. (accessed February 3, 2014) <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%;">8. WebMD. Meningitis. http://www.webmd.com/children/vaccines/meningitis. (accessed February 18, 2014). <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%; line-height: 1.5;">9. RCSB Protein Data Bank. Penicillin-binding protein 2B. http://www.rcsb.org/pdb/explore.do?structureId=2WAE. (accessed February 18, 2014). <span style="font-family: 'Times New Roman',Times,serif; font-size: 110%; line-height: 1.5;">10. PubChem. Ceftriaxone. https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5479530&loc=ec_rcs. (accessed February 18, 2014).