Susan Streble
December 12, 2001
Bacteria are everywhere; in and on our bodies and on every thing that we touch. Many species of bacteria cause a wide range of illnesses, with many different symptoms. With the discovery of antibiotics, bacterial infections are not as deadly as they used to be. Penicillin is an antibiotic that has saved many lives since it was discovered. But today it is not as useful as when it was discovered. Penicillin was once used to treat many different bacterial infections, but because of resistance, it is no longer as effective.
Alexander Flemming discovered the antibiotic penicillin in 1928. Flemming was doing research on the bacteria that causes a staph infection. He forgot to clean a petri dish with the staph bacteria on it and left it out. When he returned to his laboratory, he found the dish and noticed that a ring of mold had grown on it. Where the mold had grown, he noticed that the staph bacteria had died. He then began his work on developing the antibiotic penicillin (Huemer and Challem 1997). Initially after this discovery, not much was done with the penicillin. The first person ever to receive penicillin was a man with blood poisoning. He received doses of penicillin and his health began to improve. But at this time, it was hard to culture the penicillin and there was not enough to give the sick man. Because the doses stopped, the man’s symptoms worsened and he died.
The next chance to show what penicillin could do was in 1942 when a dance club in Boston caught on fire. Many people were burned and penicillin was used to treat infections in the victims (P. Offit, B. Offit, and Bell 1999). During World War II, penicillin was mass-produced and used to treat soldiers in the war. This was the first time penicillin was used successfully and afterwards became well known and widely used ("The Story of an Antibiotic" 2001).
There are now 50 antibiotics that are classified as penicillin (B. Zimmerman and D. Zimmerman 1996). Penicillin antibiotics include phenoxymethylpenicillin, ampicillin, and amoxicillin (Huemer and Challem 1997), to name a few. These different antibiotics are just modified versions of the original penicillin (P. Offit, B. Offit, and Bell 1999). Penicillin is then split into four generations. These different generations contain many variations of penicillin, but not all of these forms are used today because of the developing resistance (Lane and Read 1999).
Penicillin kills bacteria by causing their cell walls to stop growing, so the cell dies. It does this is by resembling a protein needed for production of the bacterial cell wall. Penicillin is in the shape of a ring, called a beta-lactam ring. Bacterial walls are kept strong and healthy by peptide chains. If the cell is not able to keep repairing and producing the peptide chains, it lyses, or dies. Penicillin prevents these peptide chains from forming, killing the cell (P. Offit, B. Offit, and Bell 1999;"The Story of an Antibiotic" 2001).
To better understand how penicillin works, it helps to know more about bacteria. Bacteria can reproduce in as fast as twenty minutes, which helps explain how resistance has already evolved. Bacteria have a single chromosome, a structure that contains genetic material, and plasmids, which are circular rings of genetic material. If there is an alteration in the genetic material of the plasmid that gives the bacteria an advantage over other bacteria, it will make copies of the plasmid and pass it on to others when it reproduces (Huemer and Challem 1997). Because bacteria reproduce so quickly, a genetic advantage would soon become present in many bacteria.
Penicillin resistance became evident in the 1940’s (Huemer and Challem 1997). Bacteria can be resistant to penicillin in different ways. Some can break down the penicillin or they make an enzyme to disguise themselves from it (B. Zimmerman and D. Zimmerman 1996). Staph bacteria developed the ability to cut the beta-lactam ring or the shape of the penicillin. After this resistance was discovered, the beta-lactam ring was altered in 1960 so that the staph bacteria were no longer resistant. This brought about a new form of penicillin called methicillin, but resistance soon started to show and this antibiotic was altered again to create vancomycin (P. Offit, B. Offit, and Bell 1999).
Normal bacterial cells have single muropeptides in their
cell walls, which help keep it strong. Because the muropeptides are single,
the penicillin could easily bind to the bacteria’s cell wall and kill it.
But some bacteria acquired branched muropeptides, which prevent the penicillin
from easily binding to the cell wall. Another way that bacterium are resistant
is by rebuilding their penicillin binding proteins or PBPs. Penicillin
targets the PBPs of the bacteria because they are needed to help build
the cell wall of the bacteria. Without the PBPs, the bacteria will die.
Some bacteria can rebuild the PBPs that are necessary for its survival
("Novel Penicillin-Resistant Gene"). This picture depicts the single and
branched muropeptides ("Novel Penicillin-Resistance"). http://www.rockefeller.edu/pubinfo/tomasz042500.nr.htm
An important discovery was made by Sergio Filipe, Ph. D and Alexander Tomasz, Ph. D in 1980. They discovered two genes that code for branched muropeptides; murM and murN. They found that bacteria that are resistant have these genes activated. If the genes are inactivated, the bacteria are no longer resistant. They also found that in order for the penicillin to be resistant it is necessary to have the activated murM and murN genes as well as altered PBPs. This was a very important discovery because it opened up the option of creating a new antibiotic. Since it is now known what genes affect resistance, an antibiotic could be given along with penicillin that would inactivate or shut off the murM and murN genes. This prevents the branched muropeptides from forming and allow the penicillin to bind to the cell wall of the bacteria ("Novel Penicillin-Resistance")
There are many bacteria that are now resistant to penicillin. "From 1989 to 1991 the proportion of resistant isolates rose in the U.S. dramatically from 0.02% to 1.3% ("Penicillin Resistance"). Some of them are Staphylococcus aureus, Streptococcus pneumonia, and the bacterium that cause syphilis, gonorrhea, and gangrene. So far, no resistance has been found in the strep bacteria. "Ninety percent of S. aureus strains are resistant to penicillin-family antibiotics . . ." (Huemer and Challem 1997). S. pneumoniae was found to be resistant in 1960 and staph began to show resistance in 1945 (P. Offit, B. Offit, and Bell 1999).
Many different factors brought about penicillin resistance. After penicillin started being mass-produced in the 1950’s, it could be purchased without a prescription. This contributed to resistance because any one could go and buy penicillin, regardless if they needed it or not. Someone could take penicillin for an illness it cannot cure. Many people confuse viral infections with bacterial infections because their symptoms can be very similar. Antibiotics are not effective towards viral infections, so if people take penicillin when they have a viral infection, they are helping the bacteria evolve resistance. Once resistance started to show, penicillin was available only with a doctor’s prescription (P. Offit, B. Offit, and Bell 39 1999). After penicillin was available only with a prescription, doctors still over-prescribed for it, giving out penicillin more often than needed. Since so much penicillin was used, the few bacteria that developed a resistance were favored and selected for (B. Zimmerman and D. Zimmerman 1996). As quoted in The Guide to Beating Supergerms from Natural Health magazine, "By taking antibiotics, you are constantly taking out the weaker bacteria and selecting for the stronger ones." By 1980, no one was researching for new antibiotics, which meant that bacteria just became more and more resistant to penicillin (Huemer and Challem 1997).
Contributing to the overuse of penicillin, in the 1940’s penicillin was used to treat gonorrhea. Prostitutes in other countries would receive monthly injections of penicillin to prevent the spread of gonorrhea. Most of the time, they were probably receiving the penicillin when they were not sick and did not need it, so resistance began to develop in gonorrhea bacteria (P. Offit, B. Offit, and Bell 1999).
Meat eaten from livestock that received penicillin also contributes to resistance in humans. Livestock are regularly injected with penicillin to prevent disease and enhance growth. If the cattle have E.coli, for example, and then someone eats the infected meat, it may be hard to treat if the person who got sick from it. The E.coli from the cattle already may have developed some resistance from the penicillin, so when the human is treated with penicillin after they eat the meat, it will be hard to cure because the bacteria are already resistant (Huemer and Challam 1997).
Many studies have been done in the United States and other countries around the world to see just how resistant some bacteria are. There is a scale that is used to measure resistance: Minimal Inhibitory Concentration, or MIC. "Resistant strains are categorized into intermediate (MIC 0.1-2.0 ug/ml) and highly resistant (MIC greater then 2.0 ug/ml)" ("Penicillin Resistance"). "The annual prevalence of penicillin resistance . . . among S. pneumoniae isolates in New York City increased from 7.2% in 1993 to 15.1% in 1995; the percentage with high-level resistance . . . increased from 1.5% to 6.3% in 1995" ("Penicillin-Resistant Streptococcus pneumoniae").
http://www.nfid.org/publications/clinicalupdates/id/pneumococcal.html
http://www.hc-sc.gc.ca/hpb/lcdc/publicat/ccdr/96vol22/dr2219ea.html
The chart above summarizes the data from a study done in Canada at different children’s hospitals to test Pneumococcal bacteria for resistance. It showed that 2.8% of 344 people tested had resistance to penicillin ("Invasive Pneumococcal Isolates").
Different groups of people are at higher risk of getting sick from resistant bacteria. Out of all places that show the highest resistance, hospitals are at the top. There are many people that are sick in the hospitals, many different bacteria are being spread, and large amounts of antibiotics being given to patients. The bacteria are spread very easily from patient to patient, and since there are different antibiotics being used, the bacteria develop multi-drug resistance very quickly (Huemer and Challem 1997).
Another group that is at high risk are white upper- and middle-class families, especially children. Upper- and middle-class families are more likely to take their children to the doctor when they are sick. If the children are going to the doctor more often, they are more likely to be prescribed penicillin or another antibiotic when they do not need it, like when they have a viral infection. Also, wealthier children are more likely to be put in daycare. If a sick child is in daycare, they are going to spread the bacteria easily to other children there. As mentioned before, they are also more likely to go to the doctor for medication. So bacteria that are more likely to be resistant because of antibiotic use will be spread between the children in day care (P. Offit, B. Offit, and Bell 1999).
There are different measures that should be taken to help prevent any further resistance from developing or to stop resistance all together. First, doctors should only prescribe medications when they are needed, like for bacterial infections, not viral infections. Second, the use of penicillin should decrease or stop altogether. Gradually bacteria that are not resistant will be more common then bacteria that are resistant. This would happen because many bacteria have to use more of their energy to make a protein that helps them be resistant. When antibiotics are stopped, the number of people with resistant bacteria in their bodies drops. If there is no penicillin present to kill of the non-resistant bacteria, they will be selected over the resistant bacteria because they are not wasting energy making a protein they do not need. Also, the amount of penicillin given to livestock needs to be decreased (P. Offit, B. Offit, and Bell 1999). There are also some alternatives to penicillin, even though penicillin is still the best treatment for some bacterial infections. Sandalwood oil can be used to treat laryngitis and soar throats and garlic could be used to treat wound and throat infections (B. Zimmerman and D. Zimmerman 53; Heumer and Challem 1996). Those at high risk of aquiring a resistant strain should be vaccinated to prevent the infection ("Pneomococcal Resistance").
Penicillin resistance is not just a problem in one area, it is a problem all over the world. Resistance resulted from unnecessary use and overuse of penicillin. Now, there are many different bacteria that are resistant to penicillin, which makes it an even bigger problem. Everyone is at risk of getting sick from a resistant strain, but especially those in hospitals, white upper and middle class families, and children in daycare. Those at high risk should be vaccinated. Because resistance began to show rather quickly and it’s presence is increasing, measures need to be taken now to prevent it from going any further.
Works Cited
Heumer, Richard P. M.D., and Jack Challem. Guide to Beating The Supergerms. New York: Pocket Books, 1997.
Lane, Karen, and Linda Reed. Medications, Guide for the Health Professions 2nd Edition. Philadelphia: F. A. Davis Company, 1999.
Offit, Paul A. M.D., Bonnie Fass-Offit M.D., and Louis M. Bell, M.D. Breaking the Antibiotic Habit. New York: John Wiley and Sons, Inc., 1999.
Penicillin Resistance. 22 Jul. 1999. Virtual Hospital. 10 Nov. 2001. <http://www.vh.org/Providers/TeachingFiles/PulmocaryCoreCurric/InvasivePneumonia/05Resistance.html>
Penicillin Resistacne Among Invasive Pneumococcal Isolates at 10 Children’s Hospitals, 1991-1994. 10 Oct. 1996. Health Canada. 10 Nov. 2001. < http://www.hc-sc.gc.ca/hpb/lcdc/publicat/ccdr/96vol22/dr2219ea.html>
Penicillin-Resistant Streptococcus pneumoniae in New York City. June 1997. New York Department of Health. 10 Nov. 2001. <http://www.ci.nyc.ny.us/html/doh/html/cd/cdstpn.html>
Penicillin: The Story of an Antibiotic. The University of Edinburgh. 10 Nov. 2001. <http://helios.bto.ed.ac.uk/bto/microbes/penicill.htm>
Pneumococcal Resistance. Jan. 1998. National Foundation For Infectious Diseases. 10 Nov. 2001 <http://www.nfid.org/publications/clinicalupdates/id/pneumococcal.html>
Rockefeler Researchers Identify Novel Penicillin-resistance Gene in Pneumonia Bacteria. 25 April 2000. The Rockefeller University, 10 Nov. 2001. <http://www.rockefeller.edu/pubinfo/tomasz042500.nr.htm>
Rosenfeld, Isadore M.D. Dr. Rosenfeld’s Guide to Alternative Medicine. New York: Random House, 1996.
Zimmerman, Barry E., and David J. Zimmerman. Killer
Germs. Chicago: Contemporary Books, Inc. 1996.