VRE

=__**Disease/Drug of interest** : __ Vancomycin-Resistant Enterococcus (VRE) =

[[image:800px-Vancomycin-Resistant_Enterococcus_01.jpg width="414" height="285"]]
Figure 1: Vancomycin-Resistant Enterococci, as shown under a scanning electron microscope. The bacteria, shown in white/light grey in this image, are arranged in both small chains and pairs.

**Motivation and Background** :
As the use of antibiotics around the world and especially in the United States has increased, drug-resistant "super bacteria" have become a major concern to health professionals. Along with MRSA (methicillin-resistant staphylococcus aureus), VRE (vancomycin-resistant enterococcus) has proven to be one of the major drug-resistant bacterial strains to appear in clinical settings. VRE can be passed through contact with blood and other potentially infectious materials (urine, semen, feces, etc.) of those who are infected [1]. Infections from vancomycin-resistant enterococcus bacteria affect around 20,000 people in the United States each year and kill nearly 1,300 people, according to the Centers for Disease Control and Prevention (CDC) [2]. VRE is adapting and there have been strains that show resistance to other antibiotics, such as tetracycline and penicillin. As antibiotics continue to be used in large numbers both in America and abroad, the problem posed by drug-resistant bacteria such as VRE will increase. Especially for patients in hospitals or other health care settings, VRE can have devastating effects. For patients with open wounds, are taking immunosuppressants such as cyclosporine or have an immune disorder such as HIV, or are being treated with combinations of antibiotics, the risk for infection is substantially higher [3]. Signs and symptoms associated with VRE include urinary tract infections, blood infections and septicemia, intense fever, nausea, swelling, and death. It is important for hospitals and other health care facilities to be vigilant against VRE by using proper sterilization techniques, identifying possible outbreaks, and using proper isolation techniques with those who are infected. To treat those with VRE, it is varies on a case-by-case basis since some strains of VRE are also resistant to other antibiotics. Common antibiotics such as ampicillin and cefalexin are among those antibiotics that are used to treat VRE.

[1] Centers for Disease Control and Prevention. Healthcare-associated Infections (HAIs). Centers for Disease Control and Prevention, http://www.cdc.gov/hai/organisms/vre/vre.html (accessed Feb 7, 2016). [2] Fraser, S. Enterococcal Infections. : Background, Pathophysiology, Epidemiology, http://emedicine.medscape.com/article/216993-overview (accessed Feb 7, 2016). [3] Cho, Y. S. Result Filters. National Center for Biotechnology Information, http://www.ncbi.nlm.nih.gov/pubmed/18821407 (accessed Feb 8, 2016). [4] Fraser, S.; Brusch, J. Enterococcal Infections Treatment & Management. Enterococcal Infections Treatment & Management: Medical Care, Surgical Care, Consultations, http://emedicine.medscape.com/article/216993-treatment (accessed Feb 7, 2016). [5] National Institute of Health. ampicillin. Ampicillin, https://pubchem.ncbi.nlm.nih.gov/compound/ampicillin#section=top (accessed Feb 7, 2016). [6] National Institute of Health. Ampicillin Oral: MedlinePlus Drug Information. U.S National Library of Medicine, https://www.nlm.nih.gov/medlineplus/druginfo/meds/a685002.html (accessed Feb 7, 2016).
 * References: **

**External links:**
http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf See slide #67

=__**Target Information** : __ Penicillin-Binding Proteins (PBPs) =


 * Size ** : molecular weight of the protein- There are two types of PBPs- high molecular-weight PBPs and low molecular-weight PBPs. High-molecular PBPs have a molecular weight greater than 60 kDa or 60,000 g/mol. Low molecular-weight PBPs have a molecular weight less than 60 kDa or 60,000 g/mol [3].


 * Location ** : Bacterial Cell Wall
 * Function in a normal cell ** : Penicillin-binding proteins (PBPs) are essential in peptidoglycan synthesis. Peptidoglycan is important in forming the cell wall, making it selectively permeable, and keeping the shape of the bacteria. Without peptidoglycan, the cell wall cannot be formed without major defects and most likely, the cell will fall apart and die [3].

=__**Drug Information**** : **__** Ampicillin **=


 * Schematic figure o **** f drug ** : Ampicillin is a beta-lactam antibiotic. These antibiotics work by binding to the penicillin-binding proteins (PBPs), which causes a conformational change that prevents the cell-wall from forming. This occurs because PBPs are essential in synthesizing peptidoglycan, the major component of bacterial cell walls. Since they are unable to form complete and functional cell walls, the bacterial cells die [3].

Figure 2: How ampicillin works. Ampicillin and other beta-lactam antibiotics work by binding PBPs, which can lead to cell death by inhibiting peptidoglycan formation.

Figure 3: The structure of ampicillin. Ampicillin has a carbon ring and has the molecular formula of C 16 H 19 N 3 O 4 S.
 * Formula ** : C 16 H 19 N 3 O 4 S


 * Molecular weight ** : 349.405 g/mol
 * CAS Number ** : 69-53-4

Figure 4: Ampicillin oral tablets. The tablets are distinguishable by the "Amp 500" written on the tablet.

Serious side effects that need to be reported immediately to medical professionals include shortness of breath, hives, vaginal infections, and serious skin rashes [4].
 * Delivery method ** : Oral, intravenous
 * Side effects ** : Nausea, vomiting, diarrhea, skin rash
 * Other names ** : Aminobenzylpenicillin, principen, amcill
 * Maker or company ** : GC Hanford Manufacturing Company
 * Is it patented ** ? Yes, it was patented by the British manufacturer Beecham, but the patent has expired and generic ampicillin can be found [5].
 * Clinical Trials Info ** : Clinical trials have been shown to prove the efficacy of ampicillin with regards to killing many strains of VRE. It is unclear exactly when the first clinical trials occurred but ampicillin's efficacy in treating many strains of VRE was known sometime in the late 1980s or 1990s [5].

__** Origin ** : __


 * Alternatives to this drug ** : Other drugs that have been used to treat VRE include ceftaroline, ertapenem, cefepime, and ceftriaxone [6].

Yes, ampicillin has been used for treatment other than in just treating VRE. Ampicillin has been shown to be effective in treating urinary tract infections, wound infections, and ear infections against bacteria that are not resistant to ampicillin.
 * Miscellaneous ** : Ampicillin is in the -cillin class of antibiotics along with penicillin and amoxicillin, among others.
 * Other uses ** : can this drug be used to treat other diseases/conditions?