Therapy and Prevention of Bacterial Diseases

Question 1

What are antiseptics?

Answer 1

Chemical agents that are applied to living tissues to kill or inhibit the growth of microorganisms.

These compounds are used for washing hands or treating surface wounds.

Question 2

What are disinfectants?

Answer 2

Disinfectants are chemical agents used on inanimate objects to kill microorganisms.

Most of these agents are too toxic to be used inside the body.

Question 3

How are infectious diseases controlled?

Answer 3

For control of infectious diseases, chemical compounds known as chemotherapeutic agents are used.

These compounds can be used internally. T

Question 4

What is the key requirement of chemotherapeutic agents?

Answer 4

Selective toxicity; these compounds inhibit or kill bacteria without causing serious harm to the host.

Question 5

What are chemotherapeutic agents that are able to kill bacteria called?

Answer 5

Antibiotics.

Question 6

What are antibiotics?

Answer 6

Antibiotics are small chemical molecules that kill bacteria (bactericidal) or inhibit their growth without directly killing (bacteriostatic).

Question 7

What is a bactericidal antibiotic?

Answer 7

Small chemical molecules that kill bacteria

Question 8

What is a bacteriostatic antibiotic?

Answer 8

Small chemical molecules that inhibit bacterial growth without directly killing

Question 9

Why are antibiotics differentiated from synthetic compounds?

Answer 9

Because they were the natural products derived from microbial activity.

Many antibiotics have been modified by chemical changes carried out in the laboratory and are described as semi-synthetic antibiotics.

In the 20th century, scientists have discovered ways to make or modify antibiotics, thus making the current antibiotic field an array of natural, semi-synthetic and synthetic antibiotics.

Question 10

What is the most commonly used antibiotic in hospitals?

Answer 10

ß-lactams.

These consist of the naturally derived penicillin-like and cephalosporin antibiotics and their many semi-synthetic derivatives.

They contain a common 4-membered ring termed the ß-lactam ring.

Question 11

Which bacteria are more sensitive to antibiotics?

Answer 11

The sensitivity of microorganisms to antibiotics and other chemotherapeutic agents varies.

Gram-positive bacteria are usually more sensitive to antibiotics than Gram-negative bacteria.

Question 12

What is a broad spectrum antibiotic?

Answer 12

One that acts on both Gram-positive and Gram-negative bacteria and is more frequently used in medicine

Question 13

What is a narrow spectrum antibiotic?

Answer 13

One that acts on only a single group of organisms (which may still be useful if a broad-spectrum antibiotic fails to resolve an infection, or for special organisms like Mycobacterium tuberculosis).

Question 14

What are optimal attributes of chemotherapeutic agents?

Answer 14

• solubility in body fluids with good penetration to the infection site
• effectiveness against bacteria at a low concentration, i.e., a low minimal inhibitory concentration (MIC)
• a broad spectrum of activity i.e., activity against a broad range of bacteria. Individual antibiotics tend to vary in their activity spectrum
• low frequency of resistance development
• low rate of breakdown or excretion in the body
• low toxicity
• well-tolerated in the human body
• non-allergenic

Question 15

How can an antibiotic be useful in medicine?

Give examples.

Answer 15

For an antibiotic to be useful in medicine, it must be able to inhibit bacteria but not affect host cells.

For example, the antibiotic can target a metabolic process that is not found in the host cell, or the antibiotic can target a bacterial protein that is sufficiently different from the homologous protein in the host cell.

Question 16

List 6 ways antibiotics work, and why humans can take the without many effects on their own cells.

Answer 16

1. Interfere with bacterial cell wall biosynthesis by inhibiting transpeptidation reactions during peptidoglycan biosynthesis, e.g., the ß-lactam antibiotics. Eukaryotic cells do not have peptidoglycan.
2. Destabilize the cell membrane, e.g., polymyxins. These compounds are more toxic to humans than other antibiotics so only used as a last resort.
3. Interfere with protein synthesis by binding to the ribosome and inhibiting its function, e.g., erythromycin, tetracyclines and the new oxazolidinones (bacteriostatic drugs). Aminoglycosides like gentamicin (bacteriocidal drugs) interfere with protein synthesis but their mechanism of action is more complex. Bacteria and eukaryotic cells have distinct ribosome structures.
4. Interfere with DNA gyrase activity (DNA unwinding during replication of the chromosome), e.g., nalidixic acid, ciprofloxacin. DNA replication is different enough in bacteria vs. humans for these compounds generally to not be toxic to us.
5. Interfere with DNA-directed RNA polymerase activity inhibiting transcription, e.g., rifampin. Bacterial RNA polymerase is different enough from ours not to be toxic.
6. Interfere with folic acid metabolism, e.g., sulfonamides and trimethoprim. These processes are specific to bacteria.

Question 17

Give examples that have decimated populations earlier in the century but are now much less problematic because of antibiotic usage.

Answer 17

Cholera, pneumonia, tuberculosis and scarlet fever

Question 18

What is antibiotic resistance?

Answer 18

The acquired ability of microorganisms to resist the effects of an antibiotic to which it is normally sensitive is known as antibiotic resistance.

Question 19

All antibiotics act against all microorganisms.

True or false?

Answer 19

False.

Not all antibiotics act against all microorganisms.

Some bacteria have an intrinsic (natural) or acquired resistance to antibiotic.

Bacteria may be naturally resistant to an antibiotic because they lack the structures that the antibiotic inhibits.

For example, mycoplasmas (a causative agent of pneumonia) are resistant to penicillin because they lack peptidoglycan.

Question 20

How may bacteria modify the target of an antibiotic to develop resistance?

Answer 20

Bacteria can become resistant to a given antibiotic because of mutations that change the structure of the target site (common in bacteria that are producing the antibiotic), alter a metabolic pathway or change the permeability of the outer membrane.

These mutations typically occur naturally during DNA replication, when ‘mistakes’ are made that actually benefit the bacteria in the presence of an antibiotic.

These mutations are then passed to the progeny of the cell (vertical gene transfer) during cell division to create a larger pool of antibiotic resistant bacteria.

Question 21

What are resistance genes?

Answer 21

Some bacteria carry specific genetic information (‘resistance genes’) that renders them resistant to the antibiotic they produce; for example, they may have a gene that encodes an enzyme that can modify the antibiotic by breaking a bond or by adding a phosphate group.

Question 22

Describe how sensitive bacteria can acquire resistance by several mechanisms through horizontal gene transfer.

Answer 22

conjugation- a non-chromosomal DNA element (a plasmid) carrying a resistance gene is transferred to a sensitive cell via cell-cell contact.

transduction – a bacterial virus picks up DNA from a resistant organism and transfers it to a sensitive cell. Can be chromosomal or plasmid DNA.

transformation – DNA that has a resistance gene is taken up from the environment by a sensitive strain. This can be from microorganisms of their own species or a different species.

Question 23

When does vertical gene transfer occur?

Answer 23

Note that vertical gene transfer, which occurs during normal cell division, will also pass on both chromosomal and plasmid DNA carrying a resistance gene to progeny cells.

Question 24

What are efflux pumps?

Answer 24

They are another reason a bacterium may be resistant.

Many organisms naturally possess rather nonspecific efflux pumps that transport antibiotics out of the organism before the drug can be effective.

Some Gram-negative bacteria are naturally resistant to some types of antibiotic due to a combination of poor permeability across the outer membrane combined with secondary mechanisms such as efflux and antibiotic inactivating enzymes that take advantage of the slow uptake of antibiotics into the bacterial cell.

Question 25

Does exposure to antibiotics cause bacteria to become drug resistant?

Answer 25

Exposure to antibiotics does not cause bacteria to become drug resistant. Changes in the bacterium that enable it to resist the antibiotic occur naturally as a result of mutation or genetic exchange and recombination. Exposure to the antibiotic selects for outgrowth of the bacteria that have become resistant through these natural processes.

Question 26

Are antibiotics used appropriately in clinical practice?

Answer 26

Resistance may develop in bacteria through the natural process of mutation and genetic recombination, but antibiotic abuse encourages the emergence of antibiotic resistant forms. A number of surveys suggest that antibiotics are used in clinical practice far more often that is necessary. For example, patients pressure doctors for antibiotics in the treatment of viral infections where antibiotics are completely inappropriate. Physicians sometimes succumb to the patient’s request and write prescriptions without ordering costly tests to pinpoint the patient’s illness. Data suggest that antibiotic treatment is warranted for only 20% of individuals seen for clinical infections, yet antibiotics are prescribed up to 80% of the time. Furthermore, in up to 50% of cases, the recommended doses or duration of treatment are not correct.

Question 27

Where is the largest area of antibiotic misuse?

Answer 27

The largest area of antibiotic misuse is within the agricultural industries. Statistics from 2016 indicate that in North America, approximately 80% of the antibiotics produced are used in agriculture. Up to 90% of those are not used to treat sick animals, but rather as growth-promoting agents in livestock and for the prophylactic treatment of livestock, crops and farmed fish. There is strong evidence that the use of antibiotics in agriculture results in antibiotic resistance in bacteria that can then be transferred to humans through handling these animals and food consumption.

Question 28

Describe the infection of Mycobacterium tuberculosis.

Answer 28

M. tuberculosis (TB) causes the disease tuberculosis, which often is an infection of the lungs. The organism is spread directly from person to person. M. tuberculosis induces an inflammatory reaction in the lungs, resulting in the engulfment of the bacteria by phagocytic cells. The bacteria survive and multiply inside the macrophage cells, resulting in further spread throughout the lung. Cell-mediated immunity is induced but is not completely effective in clearing the bacteria. The bacteria tend to survive in the lungs, in a dormant state. Reactivation of the disease (reasons poorly understood) can lead to rapidly progressing, often fatal infections.

Question 29

Are there any consequences to antibiotic use?

Answer 29

Side effects are inherent in all drugs. The side effects of an antibiotic can range from mild (e.g., drowsiness, nausea, cramps) to severe (e.g., toxicity to internal organs or hearing loss after prolonged use of certain antibiotics). In very rare cases, the side effects can be fatal (e.g., allergy to penicillin). Treatment of a bacterial infection with antibiotics can destroy both the microbiota as well as pathogenic bacteria. For example, when an antibiotic is given orally, some members of the intestinal microbiota may be affected and opportunistic pathogens may be able to establish themselves in the gastrointestinal tract. This can result in disruption of normal digestive functions or diarrhea. When antibiotic administration is discontinued, the microbiota of the gastrointestinal tract is eventually re-established.

Question 30

What are superbugs?

Answer 30

A global crisis! New superbugs that are resistant to most or all types of antibiotic treatment have arisen (e.g., MRSA: methicillin-resistant Staphylococcus aureus, VRE: vancomycin-resistant Enterococcus; imipenem resistant Pseudomonas aeruginosa, penicillin resistant Streptococcus pneumoniae). These superbugs are resistant to many different antibiotics.

Question 31

What is the most common multiple-drug resistant pathogen in hospitals?

Answer 31

MRSA has now become the most common multiple-drug resistant pathogen in hospitals, and many MRSA cases are untreatable with any of the readily available antibiotics.

Question 32

What is Vancomycin?

Answer 32

Vancomycin is a glycopeptide that acts by interfering with the synthesis of the bacterial cell wall. It is a very important antibiotic. Vancomycin is often referred to as the ‘antibiotic of last resort’; the last antibiotic to be used to retreat bacteria infections that are resistant to many other antibiotics. **Several cases of vancomycin resistant staphylococcal and streptococci infections have been reported since 1996.**

Question 33

What is a vaccine?

Answer 33

Vaccines are an important application of immunology. A vaccine is a suspension of microorganisms or parts of microorganisms that are used to induce immunity by injection or exposure by the more typical portal of entry (e.g., ingestion of a vaccine). **Vaccines prevent disease, but not infection.** Vaccines work by inducing the primary immune response, such that subsequent exposure to the pathogen induces a faster and more vigorous immune response that limits the growth of the pathogen. Vaccines may be administered prior to exposure to the pathogen, or after exposure to the pathogen but before the occurrence of disease. Along with improved sanitation, vaccines have contributed significantly to reduced infectious disease-induced mortality

Question 34

What are the materials used in vaccines typically made of?

Answer 34

* killed virulent bacteria * avirulent mutants of pathogenic bacteria * the outermost components of the microorganism, e.g., capsules, surface-exposed proteins * toxoids, e.g., denatured (or inactivated) toxins

Question 35

What may immunity to pathogens be due to?

Answer 35

**active immunization** – which involves injecting the vaccine into humans to induce a specific immune response, i.e., an antibody or cellular immune response. Active immunization usually occurs at the level of a whole society or population. **passive immunization** - which involves injecting pre-formed antibodies raised against a specific bacteria/bacterial component into an infected person. This is not currently done in humans although hyper-immune gamma globulin is used for some illnesses (e.g., emergency treatment after exposure to botulism toxin).

Question 36

Describe the prevalence of Mycobacterium tuberculosis.

Answer 36

One-quarter of the world’s population is infected with TB. Approximately 10,000 cases were reported in 2016 in the U.S. The disease is especially prevalent in poor people and AIDS patients living in large American cities, e.g., New York. M. tuberculosis is responsible for approximately 5% of all deaths in developing countries, and it killed at least 1.7 million people worldwide in 2016. This is the highest number of deaths which can be attributed to a single infectious agent.

Question 37

Describe vaccination for Mycobacterium tuberculosis.

Answer 37

The vaccine for tuberculosis is a live strain of Mycobacterium bovis (BCG) that is immunologically similar to, i.e., shares antigens with, M. tuberculosis. Vaccination results in a cell-mediated immune response against M. tuberculosis. The effectiveness of this vaccine has been questioned.

Question 38

Describe treatment of Mycobacterium tuberculosis.

Answer 38

The antibiotic regime for M. tuberculosis requires long-term therapy for 9–12 months, often with multiple antibiotics. Widespread resistance has already developed to one of the main antibiotics used, namely isoniazid, and some patients carry multi-resistant strains that are resistant to all 8 front line antibiotics in use. This has resulted in an increased mortality.