Bacterial Infection

Introduction

While children's recurring ear infections used to be easily treated, lately they have become a parent's nightmare. In the old days, you would simply call the pediatrician, make a quick trip to the pharmacy for the "pink stuff" - shake well, keep in the refrigerator, finish all - and in a week you had a happy, healthy child again. But now, infections seem more difficult to treat in both children and adults. What's changed?

What is it?

Bacteria are simple one-celled organisms. We share our world with countless different species of bacteria, many of which have not yet been identified. Most are harmless, and many are helpful -- even vital to our existence. For example, the bacteria that live in the roots of plants like beans and peas, help extract nitrogen from the atmosphere to enrich the soil.

Bacteria can be found, by the billions, all around us: on furniture and counter-tops, in the soil, and on plants and animals. They are a natural and needed part of life. In fact, they often protect us by competing with more dangerous bacteria for food and space. Bacteria cause disease and infection when they are able to gain access to more vulnerable parts of our bodies and multiply rapidly. Bacteria can infect many parts of the body, including:

  • eyes
  • ears
  • throat
  • sinuses
  • lungs
  • airways
  • skin
  • kidneys
  • bladder
  • stomach
  • colon
  • brain
  • heart
  • bones
  • genitals
  • blood

What causes it?

Bacteria cause disease in two ways: they release toxins that harm and kill body cells, and they provoke the immune system, leading to inflammation, which can in itself be harmful.

Bacteria release toxins that enter cells and kill them.

The body's first reaction to a bacterial invasion, as in any injury, is a general inflammatory reaction. Blood vessels in the area of the infection widen to increase the supply of white blood cells that fight infection. Blood proteins, called complement, are released into the system. Complement either kills the bacteria directly or attracts immune cells called phagocytes, which ingest and kill the bacteria. The body then produces more immune cells, including white blood cells called T cells, which kill foreign substances in the body. T cells stimulate other white blood cells called B cells to secrete specific antibodies. Antibodies are molecules that the body's immune system uses to identify a particular invader. Over a person's lifetime, the immune system develops millions of antibodies. In response to a bacterial invasion, the antibodies bind to bacteria and then attract complement and phagocytes, which kill the bacteria.

When bacteria enter the body and multiply, the body's first defense is inflammation.

Fever enhances the body's defense mechanisms. Blood is moved into the interior of the body, to reduce heat loss. Then, when heat regulating mechanisms return to normal, the body reduces its temperature by returning blood to the skin and perspiring. Chills may result.

In many cases, the body's own defense mechanisms are capable of repelling attacks by invading microorganisms, like bacteria and viruses. When the bacteria succeeds in multiplying to the point where the body's natural defenses are not adequate, antibiotics may be needed to either destroy the bacteria completely, or else kill enough of them so that the immune system can finish the job.

Who has it?

Bacterial infection affects all people at some point in their lives. It is hard to estimate how many cases of bacterial infections there are at any given time, because so many different types of bacteria are involved. Bacterial infections are more common among children, the elderly and those with other health problems. In the general population, the rate of infectious disease has been curbed dramatically by improved sanitation and the introduction of drugs that treat and prevent infection.

Because of their potential threat to public health, the rates of infection by more dangerous, drug resistant bacteria are monitored by organizations like the federal Centers for Disease Control and Prevention. These kinds of infections are increasing. Researchers have estimated, for example, that the incidence of infections that do not respond to the antibiotic vancomycin, increased by a factor of 20 in intensive care units in the United States between 1987 and 1993. Vancomycin was once considered the last resort in the battle against infectious bacteria. Recently, two new antibiotics, linezolid (Zyvox) and quinupristin/dalfopristin (Synercid) have been introduced. These agents currently remain last resort to resistant bacteria. Their use is being carefully controlled to prevent microorganisms from developing resistance.

It is important for the medical community to stop prescribing unnecessary antibiotics, and for the public to stop asking for them. The emergence of bacteria that can thrive in the presence of some of the most powerful antibiotics poses a dangerous threat to public health. The consequences for society are also costly. As more and more bacteria become resistant to current therapies, patients have to take newer and more expensive antibiotics and society has to spend more time and money trying to develop new and better agents. It can cost over $5,000 to treat a patient with a resistant bacterial infection. According to one estimate this adds up to a total of more than $4 billion spent each year in the United States to treat multi-drug resistant bacterial infections.

Bacterial Resistance

Since Alexander Fleming discovered the antibiotic properties of the penicillin mold in 1929, two parallel processes have been unfolding. One is a marked drop in deaths due to infectious diseases. The other has been a dramatic demonstration of survival of the fittest. With increasing swiftness, disease-causing bacteria have become resistant to common antibiotics. Fears are growing that bacteria resistant to vancomycin, long considered the antibiotic of last resort, will soon emerge. These kinds of infections are usually found among seriously ill hospital patients, but even in the case of less serious infections, doctors are finding that even newer antibiotics are becoming less effective. Therefore, finding drugs that will work against resistant bacteria, or use novel mechanisms that make them less vulnerable to the development of resistance, are the primary focus of many researchers.

HOW DO BACTERIA BECOME RESISTANT?
There are various ways in which bacteria evolve so that they can avoid the effects of an antibiotic. Some acquire genes that direct the assembly of enzymes that are capable of degrading antibiotics, or can chemically modify, and thus inactivate the drugs. In other cases, resistance genes cause bacteria to alter or replace molecules that the antibiotic normally binds to. Without these binding points, the antibiotic cannot perform its function. Bacteria may also do away with entry ports for a particular drug, and have even been capable of developing molecular pumps that expel the antibiotic from inside the cell before the medicines have had a chance to find their targets.
Bacteria resist antibiotics by developing mechanisms such as pumps, enzymes or resistant genes.

Armed with this knowledge, scientists are working on approaches that can revive the effectiveness of existing antibiotics. For example, many bacteria evade penicillin and its relatives by switching on an enzyme, penicillinase, which degrades those compounds. An antidote already exists that inhibits the action of penicillinase. This prevents the breakdown of penicillin and so frees the antibiotic to work normally. Scientists at Tufts University have developed a compound that jams the microbial pump that ejects tetracycline from bacteria; with the pump inactivated, tetracycline can penetrate bacterial cells effectively.

NEW APPROACHES TO ANTIBIOTIC RESISTANCE
Responding to growing concerns about the looming danger of disease-causing bacteria that are impervious to the most potent antibiotics, researchers are using a variety of tactics to address the problem.

One is to use sophisticated microscopic techniques and computer software to understand the molecular structure of antibiotics and the enzymes and toxins bacteria use to invade cells and evade antibiotics. At the University of Pennsylvania Medical Center, for example, researchers used x-ray crystallography to solve the structure of vancomycin, which is presently considered the antibiotic of last resort to fight selected serious bacterial infections.

Researchers also seek out metabolic processes that are present in plants, fungi and bacteria, but are not found in vertebrates. In this way, they can develop compounds that inhibit enzymes in the process, or pathway, without causing side effects in humans.

They have found, for example, that particular disease-causing strains of enterococci produce large amounts of a substance called cytolysin. A bacterial toxin, cytolysin breaks down cell membranes, enabling the bacteria to invade other bacterial and mammalian cells. For decades, researchers have been studying how cytolysin is manufactured. They have found several points in the process where it may be possible to inhibit the enzymes involved. A drug that inhibits the activation of cytolysin could prevent the bacteria from multiplying without damaging other bacteria. This kind of compound would also not encourage the development of antibiotic resistance because it would not act directly on the organism.

Genomic research, or study of bacterial genes, is also helping researchers develop more targeted antibiotics. Rather than screening known families of chemical compounds, they are studying bacterial genes, which contain the information that tells a microbe how to cause disease. For example, researchers may be able to prevent Psuedomonas aeruginosa from colonizing the lungs by finding a drug that works against the gene that allows Pseudomonas to attach itself to the lung surface.

What are the risk factors?

If you have any of the following, you are at risk for a bacterial infection:

  • skin abrasions
  • breaks in mucous membranes
  • inadequate sanitation
  • lack of vaccinations
  • surgery or chemotherapy
  • a weakened immune system, either from medications or diseases, such as cancer or AIDS

What are the symptoms?

Common signs and symptoms of bacterial infection include:

  • an elevated body temperature
  • sweating
  • chills
  • confusion
  • increased pulse rate
  • fast breathing
In addition, people who have bacterial infection often have elevated numbers of circulating white blood cells in their blood stream. People may also have other symptoms of infections depending on the location of the infection.

How is it treated?

The selection of an antibiotic to treat an infection will depend on several factors. These include the site of the infection, the bacteria causing the infection, and allergies you have to various antibiotics. In addition, other considerations include the severity of the infection, what drugs have been used to treat similar infections for you in the past, and knowledge of what antibiotics have successfully treated a given infection in your area of the country.

Regardless of the drug chosen, it is important to remember to take the entire antibiotic prescribed by your physician. Many people take their medication only until they feel better. This can allow an infection to recur with even greater severity in the near future. It can also have the potential to prevent a given antibiotic from working well to treat other patients with the same infection in your family or community.

Each class of antibiotics may be used for a variety of infections.

Helping Yourself

The U.S. Centers for Disease Control and Prevention estimates that one third of all the antibiotics prescribed each year - 150 million of them--are unnecessary. By taking antibiotics more often than you need to, your body can develop a resistance to the drugs, making them useless when you do get a bacterial infection. The more resistant bacteria become, the more difficult it will be to treat them in the future.

So one of the best ways to protect yourself against bacterial infections is not to ask your doctor for an antibiotic when you have a virus - a cold or flu, for example. In the case of a virus, antibiotics will not help you get better and may make you worse - if you have an adverse reaction to the medication. Therefore, when you have a virus, drink plenty of fluids, get lots of rest, and try over-the-counter products rather than prescription drugs.

Over-the-counter preparations that may relieve your cough or cold symptoms include:

  • aspirin, acetaminophen or ibuprofen for fever and pain - children should avoid aspirin unless specifically directed by a pediatrician
  • decongestants to open clogged nasal passageways and sinuses
  • cough liquids and drops to control coughing

As always, carefully read product labels and heed all cautions. And, get plenty of rest. Given time, your immune system will be able to do its job and get rid of the virus.

What is on the horizon?

New drugs for the treatment of bacterial infections are continuously being studied. One of the most common problems with treating patients outside of a hospital setting is making sure they finish all of their prescribed medications. Many patients begin to feel better after a few days of drug therapy and thus, quit taking their medication. However, to be fully cured most antibiotics require use for seven or more days. When patients do not finish a full course they often end-up getting the same infection again. Drug companies have been trying to create drugs that do not require use for the normal seven or more days. One drug EDP-420 is currently being tested for use in lung infections. This drug should only have to be taken for three days. Drugs such as this will help decrease the reinfection problem that we currently see.

References

ClinicalTrials.gov. Comparative Study of EDP-420 Versus Another Antibiotic in the Treatment of Community Acquired Pneumonia. http://clinicaltrials.gov/ct/show/NCT00270517?order=33. Accessed March 2007.

Mainous A., Hueston, W., Love, M. Antibiotics for colds in children. Archives of Pediatrics & Adolescent Medicine. 1998;152:349-352; http://www.ama-assn.org/sci-pubs/journals/ archive/ajdc/vol_152/no_4/poa7438.htm; Archives of Pediatrics & Adolescent Medicine

Levy S. The challenge of antibiotic resistance. http://www.sciam.com; Scientific American. Accessed April 2006

McManus M. Mechanisms of bacterial resistance to antimicrobial agents. American Journal of Health-System Pharmacy 1997;54(12):1420-33

Rybak M, McGrath B. Combination antimicrobial therapy for bacterial infections. Drugs 1996;52(3):390-405

Nyquist A, et al. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. Journal of the American Medical Association 1998;279(11):875

Schrag SJ, Pena C, Fernandez J, et al. Effect of Short-Course, High-Dose Amoxicillin Therapy on Resistant Pneumococal Carriage. JAMA. 2001;285:49-56.

Siegel JD et al. The Healthcare Infection Control Practices Advisory Committee. Management of Multidrug-Resistant Organisms In Healthcare Settings, 2006. Released Oct 2006. Available at http://www.cdc.gov/ncidod/dhqp/ar_mrsa_spotlight_2006.html. Accessed March 2007.

Bacterial Infection Health Condition Last Updated: March 2008

Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.

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