Bacterial Resistance to Antibiotics

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Bacterial Resistance to Antibiotics (page 1)

(This chapter has 4 pages)

© Kenneth Todar, PhD

Introduction

In the past 60 years, antibiotics have been critical in the fight against infectious disease caused by bacteria and other microbes. Antimicrobial chemotherapy has been a leading cause for the dramatic rise of average life expectancy in the Twentieth Century. However, disease-causing microbes that have become resistant to antibiotic drug therapy are an increasing public health problem. Wound infections, gonorrhea, tuberculosis, pneumonia, septicemia and childhood ear infections are just a few of the diseases that have become hard to treat with antibiotics. One part of the problem is that bacteria and other microbes that cause infections are remarkably resilient and have developed several ways to resist antibiotics and other antimicrobial drugs. Another part of the problem is due to increasing use, and misuse, of existing antibiotics in human and veterinary medicine and in agriculture.

In 1998, in the United States, 80 million prescriptions of antibiotics for human use were filled. This equals 12,500 tons in one year. Animal and agricultural uses of antibiotics are added to human use. Agricultural practices account for over 60% of antibiotic usage in the U.S., so this adds an additional 18,000 tons per year to the antibiotic burden in the environment.

Nowadays, about 70 percent of the bacteria that cause infections in hospitals are resistant to at least one of the drugs most commonly used for treatment. Some organisms are resistant to all approved antibiotics and can only be treated with experimental and potentially toxic drugs. An alarming increase in resistance of bacteria that cause community acquired infections has also been documented, especially in the staphylococci and pneumococci (Streptococcus pneumoniae), which are prevalent causes of disease and mortality. In a recent study, 25% of bacterial pneumonia cases were shown to be resistant to penicillin, and an additional 25% of cases were resistant to more than one antibiotic.

Microbial development of resistance, as well as economic incentives, has resulted in research and development in the search for new antibiotics in order to maintain a pool of effective drugs at all times. While the development of resistant strains is inevitable, the slack ways that we administer and use antibiotics has greatly exacerbated the process.

Unless antibiotic resistance problems are detected as they emerge, and actions are taken immediately to contain them, society could be faced with previously treatable diseases that have become again untreatable, as in the days before antibiotics were developed.

History of antibiotics and emergence of antibiotic resistance

The first antibiotic, penicillin, was discovered in 1929 by Sir Alexander Fleming, who observed inhibition of staphylococci on an agar plate contaminated by a Penicillium mold. Fleming was searching for potential antibacterial compounds. He noticed that a patch of the mold Penicillium notatum had grown on a plate containing the bacterium Staphylococcus and that around the mold there was a zone where no Staphylococcus could grow. After more research, he was able to show that culture broth of the mold prevented growth of the Staphylococcus even when diluted up to 800 times. He named the active substance penicillin but was unable to isolate it.

In the center of the plate is a colony of Penicillium notatum, a mold that produces penicillin. After appearance of the mold colony, the plate was overlaid with a bacterial culture of Micrococcus luteus which forms a yellow "lawn" of growth. A zone of inhibition of bacterial growth surrounds the fungal colony where penicillin has diffused into the medium. http://helios.bto.ed.ac.uk/bto/microbes/penicill.htm#Top

Several years later, in 1939, Ernst Chain and Howard Florey developed a way to isolate penicillin and used it to treat bacterial infections during the Second World War. The new drug came into clinical usage in 1946 and made a huge impact on public health. For these discoveries Fleming, Chain and Florey were awarded the Nobel prize in 1945. Their discovery and development revolutionized modern medicine and paved the way for the development of many more natural antibiotics.

While Fleming was working on penicillin, Gerhard Domagk, a German doctor, announced the discovery of a synthetic molecule with antibacterial properties. He named the compound Prontosil, and it became the first of a long series of synthetic antibiotics called sulfonamides or sulfa drugs. Prontosil was introduced to clinical use in the 1930s and was used to combat urinary tract infections, pneumonia and other conditions. While sulfa drugs in many cases are not as effective as natural antibiotics, they are now in widespread use for the treatment of many conditions. Gerhard Domagk was awarded the Nobel prize in 1939 for his discovery of Prontosil.

In 1946, penicillin became generally available for treatment of bacterial infections, especially those caused by staphylococci and streptococci. Initially, the antibiotic was effective against all sorts of infections caused by these two Gram-positive bacteria. Penicillin had unbelievable ability to kill these bacterial pathogens without harming the host that harbored them. It is important to note that a significant fraction of all human infections are caused by these two bacteria (i.e., strep throat, pneumonia, scarlet fever, septicemia, skin infections, wound infections, etc.).

In the late 1940s and early 1950s, new antibiotics were introduced, including streptomycin, chloramphenicol and tetracycline, and the age of antibiotic chemotherapy came into full being. These antibiotics were effective against the full array of bacterial pathogens including Gram-positive and Gram-negative bacteria, intracellular parasites, and the tuberculosis bacillus. Synthetic antimicrobial agents such as the "sulfa drugs" (sulfonamides) and anti-tuberculosis drugs, such as para aminosalicylic acid (PAS) and isoniazid (INH), were also brought into wider usage.

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