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.
Tetracycline is an antibiotic group that works by preventing the growth and spread of bacteria, and they are named for their 4 hydrocarbon rings. Tetracyclines are used primarily for treating infections as well as controlling acne and rosacea (1). The 6 members of the tetracycline group are oxytetracycline, tetracycline, demeclocycline, methacycline, doxycycline, and minocycline (2). Once inside the bacterial cell wall, tetracyclines bind reversibly to the 30S ribosomal subunit to block the binding of the aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex (2). Blocking translation will cause a stoppage of protein synthesis in the bacteria cell. A unique side effect for tetracyclines is phototoxicity, or an increased risk of sunburn. Other side effects of taking this antibiotic include itching of the rectum or vagina, sore mouth, changes in skin color, severe headache, blurred vision, and dark-colored urine (1). Tetracyclines used to be helpful for a variety of bacterial problems, but resistance buildup by bacteria has changed that. Bacteria have used two main types of resistant mechanisms: tetracycline efflux and ribosomal protection. Efflux is responsible for moving toxic substances, such as antibiotics, out of the cell. An animation of how efflux is done can be seen in the video below. Ribosomal protection protein Tet(O) is a translational GTPase with high similarity to the elongation factor EF-G. This will "protect" the ribosome from binding with the tetracycline antibiotic during translation (3). Efflux resistance genes are generally found on plasmids, whereas genes involved in ribosome protection have been found on both plasmids and conjugative transposons (both are transmissible elements). Tetracyclines are excreted via urine and feces into the environment, creating estrogen effects and antibiotic resistant microorganisms (4).
References:
1. "Tetracycline: MedlinePlus Drug Information." U.S National Library of Medicine. U.S. National Library of Medicine, n.d. Web. 19 Oct. 2013. 2. May, Byron. "Tetracyclines." Tetracyclines. N.p., n.d. Web. 19 Oct. 2013. 3. Li, Wen. Mechanism of Tetracycline Resistance by Ribosomal Protection Protein Tet(O). N.p., July 2012. Web. 19 Oct. 2013. 4. Daghrir, R. "Tetracycline Antibiotics in the Environment: A Review." Environment Chemistry Letters. N.p., Sept. 2013. Web. 11 Nov. 2013.
Antibiotics have been used increasingly over the last 50 years in animal feed for a couple of reasons. The antibiotics act as an anti-microbial agent as well as a growth-promoting agent. There are now a dozen antibiotics put into animal feed, including chlorotetracycline, procaine penicillin, oxytetracycline, tylosin, bacitracin, neomycin sulfate, streptomycin, erythromycin, linomycin, oleandromycin, virginamycin, and bambermycins (1). These twelve antibiotics are of microbial origin, and on top of these there are other chemically synthesized antimicrobial agents. The three main groups of chemically synthesized antibiotics are arsenical, nito-furan, and sulfa compounds.
Antibiotics are used in animal feed at a rate of 2-50 grams per ton for improved performance of animals. The rate increases to 50-200 grams per ton when specific diseases are being targeted. From 2009-2011, 72 percent of all United States sales of antimicrobials comprised of those routinely added to water or animal feed (2). There are major benefits from antibiotics, including increased efficiency and growth rate, treating clinically sick animals, and greatly reducing the incidence of infectious disease. There are a lot of risks with using this amount of antibiotics in feed, however. After being fed this food filled with antibiotics, the animals start to retain the strains of bacteria that are resistant to antibiotics (2). The resistant bacteria are then transmitted to other animals, and the resistant bacteria do well in the intestinal flora of the animals. The three main ways bacteria can exchange genetic material with other bacteria are transformation, conjugation, and transduction. All three of these ways of exchanging genetic material can change genomes and create new, more powerful strands of resistant bacteria. Humans can become infected with the bacteria too, mostly from interaction and contact with the infected animals' feces or by eating the infected meat.
1. "Effects of Antibiotics on Animal Feed." N.p., 1998. Web. 10 Oct. 2013. 2. Wallinga, D. "Do Antibiotics in Animal Feed Pose a Serious Risk to Human Health?"ScienceDaily. ScienceDaily, 11 July 2013. Web. 19 Oct. 2013.
Cephalosporins are a group of beta-lactam antibiotics derived from the mold Cephalosporium. Beta-lactam antibiotics all contain a four membered beta-lactam ring with three carbons and a nitrogen, as well as a carbonyl group off one of the carbons. There are three groups: Cephalosporin N,C, and P. These three groups all have a slightly similar chemical makeup. Cephalosporin N and C are chemically related to Penicillins, and Cephalosporin P is a steroid related to fusidic acid. They act in the same manner as Penicillins in the fact that they disrupt bacterial cell wall synthesis. First generation Cephalosporins are active against Gram positive bacteria, whereas later generations are more successful against Gram negative bacteria (1). Some examples of these antibiotics are Cefamandole, Cefurxiome, Cefonicid, and Cefoxitin. Cephalosporins are used to treat step throat, peritonitis, diverticulitis, staph infections, bronchitis, sinusitis, pneumonia and gonorrhea (2). Cephalosporins, like all antibiotics, do not work on treating viruses. There are symptoms that come with taking Cephalosporins, including stomach cramps, nausea, vomiting, and facial flushing. These antibiotics can be taken orally intravenously, or intramuscular injection. Bacterial resistance mechanisms are possible, and there are three main mechanisms used by bacteria on cephalosporins. The first is the destruction of the beta-lactam ring by beta-lactamases. Next is altering the affinity of cephalosporins for their target site. Lastly, bacteria can cause decreased penetration of the antibiotic to the target site. This is only possible for gram-negative bacteria because gram-positive bacteria lack an outer cell membrane (3). Cephalosporins should not be combined with alcohol or taken with medicines that contain alcohol.
References: 1. "Livertox." Cephalosporins. N.p., 2011. Web. 19 Oct. 2013. 2. "CEPHALOSPORINS - INJECTION Side Effects, Medical Uses, and Drug Interactions." MedicineNet. N.p., 2013. Web. 19 Oct. 2013. 3. Itokazu, Gail. "CEPHALOSPORINS." CEPHALOSPORINS. N.p., n.d. Web. 19 Oct. 2013.
The Methicillin-resistant Staphylococcus aureus (MRSA) infection is caused by a strain of staph bacteria. This particular bacteria has become resistant to the antibiotics commonly used to treat regular staph infections, and therefore these normal antibiotics are useless. This MRSA infection can occur in hospital settings (during surgery, artificial joints, etc.) or among healthy people ( skin to skin contact). The infection starts off as a boil on the skin and gets progressively worse if not treated. Bactrim and vancomycin are often the first drugs used as antibiotics for MRSA, among others. There has not yet been an antibiotic resistance seen for these drugs, so they will continue functioning properly. Antibiotics are only one option for MRSA, as the boil can be incised and drained.
