Metronidazole is a specific antibiotic used for anaerobic bacteria and protozoa. These bacteria and parasites share an anaerobic niche in the lumen of the bowel or vagina (1). It is an imidazole derivative and acts as either an antibacterial or antiprotozoal (1). Metronidazole is known commonly by the brand name Flagyl, and it is taken orally or topically. Flagyl topical gel is used to cure rosacea, or acne, and vaginal gel is used for bacterial vaginosis. The pill has a bitter taste, so it is best taken with some type of juice. It works by killing bacteria or preventing further growth. Side effects for Flagyl are dizziness, headache, nausea, stomach pain, loss of appetite, and constipation. Flagyl also causes major problems when mixed with alcohol. Mixing Flagyl and alcohol will cause extreme nausea and vomiting. Clostridium difficile is commonly treated by Flagyl and C. difficile causes colon inflammation and diarrhea (1). Flagyl also treats against vaginal infections (bacterial vaginosis), Crohn's disease (inflammatory bowel disease), stomach ulcers (H. pylori), and Giardiasis (parasite infection in the intestines) (2). Metronidazole is inactive until it is metabolized within the host or microbial cells, and it only becomes active when it is reduced. In these bacteria or parasites, metronidazole is activated when it receives an electron from ferredoxin or flavodoxin (3). An example of bacteria inhibition is seen when Metronidazole inhibits Helicobater pylori by inhibiting the expression of Flagellin (2). Without the presence of flagella, the Helicobacter pylori become nonmotile and can no longer function. This is a prime example as to why Flagyl is so effective against stomach ulcers.
References:
1."Metronidazole (Oral Route)." Mayo Clinic. Mayo Foundation for Medical Education and Research, 01 Jan. 2012. Web. 27 Nov. 2013.
2. Kamiya, S. "Microbiology (metabolism,physiology)." Helicobacter 8 (2003): n. pag. Web. 27 Nov. 2013. 3. Samuelson, John. "American Society for MicrobiologyAntimicrobial Agents and Chemotherapy." Why Metronidazole Is Active against Both Bacteria and Parasites. N.p., n.d. Web. 27 Nov. 2013.
With a lot of bacterial strains becoming resistant to normal antibiotics, there has been a search for new antimicrobial drugs. Scientists began combining antimicrobial drugs for a synergistic effect, which made those drugs extremely effective. With the increase in technology, computers are now being used to design molecules. These molecules are being made to interact with specific microbial structures, and the most successful molecule made from a computer has been Saquinavir. Saquinavir is used in HIV therapy (antiviral), and it acts as an inhibitor for HIV protease. Protease is an enzyme that cleaves protein molecules into a bunch of smaller proteins. Stopping the protease stops HIV from virally replicating within an infected cell. The HIV protease contains catalytic aspartic acids that allow a catalytic cleavage reaction to occur (1). Saquinavir binds to the active site of HIV protease, and this binding keeps HIV dormant. It is very similar to the substrate that usually binds to the active site, but it is also different enough so it does not get cleaved by the aspartic acids. Saquinavir changes Glycine to Valine at position 48 in the HIV protease (1). It has been approved by the FDA and currently there are two formulations out on the market: Invirase and Fortovase. These drugs inhibit both HIV-1 protease and HIV-2 protease. When Saquinavir is taken with other low dose protease inhibitors (such as Ritonavir) its oral bioavailability is markedly increased (2). This allows for reduced dosing frequency and/or dosage. Some side effects of Saquinavir are diarrhea, nausea, vomiting, and tiredness.
References:
1. Perry, C.M, and S. Noble. "Saquinavir Soft-Gel Capsule Formulation: A Review of Its Use in Patients with HIV Infection." Drugs. N.p., 1998. Web. 21 Nov. 2013.
2. Figgitt, D.P., and G.L. Plosker. "Saquinavir Soft-Gel Capsule: An Updated Review of Its Use in the Management of HIV Infection." Drugs (2000): n. pag. Web. 21 Nov. 2013.
There has been a large development of bacterial disease treatment strategies other than antibiotics due to the increase in resistant bacterial strains. Resistance modifying agents are being used to inhibit bacterial resistance mechanisms such as drug efflux from the cell. An efflux inhibitor will not allow the bacteria strains to take antibiotics out of the cell. Phage therapy is also being looked at to treat bacterial infections with viruses (phages). Phage therapy is used broadly in the countries of Russia and Georgia. Bacteria can also become resistant to viruses, but it is much easier to obtain new phage for new strains of resistant bacteria than new antibiotics (1). Bacteriocins are proteinaceous toxins produced by bacteria to inhibit the growth of similar or closely related bacterial strains (2). They were first discovered in 1925 by A. Gratia while he was searching for ways to kill bacteria, which later resulted in the development of antibiotics. Chelation therapy is a type of treatment used by injecting EDTA into the bloodstream to remove metals from the body (3). This limits nutrients that bacteria can use for growth, which will restrict pathogen spread (Example: Iron). The use of probiotics can be used to treat digestive bacterial infections by inhibiting and interfering bacterial strains. Probiotics are used to maintain the natural balance of organisms in the intestines (4). Silver can also be used to disrupt bacterial cellular processes by binding to sulfur compounds, such as disulfide bond formation (5). Silver is not toxic in the body in microscopic amounts, but it is toxic in large doses. With the growing amount of antibiotic resistant bacteria, these treatment strategies may become more prevalent in the future of antibiotic usage.
References:
1. Krylov, Victor. "Genetic Approach to the Development of New Therapeutic Phages to Fight Pseudomonas Aeruginosa in Wound Infections." Academic Search Complete. N.p., Jan. 2013. Web. 11 Nov. 2013.
2. Joerger. "Alternatives to Antibiotics: Bacteriocins, Antimicrobial Peptides and Bacteriophages." NCBI. U.S. National Library of Medicine, n.d. Web. 11 Nov. 2013.
3. "Chelation Therapy." Web MD. N.p., June 2011. Web. 11 Nov. 2013.
4. "Probiotics and Antibiotics." IFFGD. N.p., n.d. Web. 11 Nov. 2013.
5. Cossins, Dan. "Silver Boosts Antibiotic Efficacy." The Scientist. N.p., n.d. Web. 11 Nov. 2013.
