Antimicrobial Chemotherapy

Question 1

What are antimicrobial drugs?

Answer 1

Antimicrobial drugs are effective in the treatment of infections because of their selective toxicity—the ability to kill an invading microorganism without harming the cells of the host.

Question 2

What is the principle of selective antimicrobial therapy?

Answer 2

Selective antimicrobial therapy takes advantage of the biochemical differences that exist between microorganisms and human beings.

The selective toxicity is relative rather than absolute, requiring that the concentration of the drug be carefully controlled to attack the microorganism while still being tolerated by the host.

Question 3

Ideal properties of an antimicrobial agent

Answer 3

1. Selective, broad spectrum, and bactericidal
2. Non-toxic to host
3. Long plasma half-life (fewer doses)
4. Good tissue distribution
5. Low plasma-protein binding
6. No interference with other drugs

Question 4

Classification of antibacterials

Answer 4

1. Chemical. e.g., Tetracycline and Aminoglycosides
2. Target site. e.g.,
   a. Cell wall inhibitors: Penicillins, Cephalosporins, and Vancomycin
   b. Cytoplasm and protein synthesis inhibitors (50S/30S): Macrolides, Aminoglycosides
   c. Nucleus inhibitors: Quinolones

Question 5

What are bacteriostatic drugs?

Answer 5

Bacteriostatic drugs arrest the growth and replication of bacteria at serum levels achievable in the patient.

They limit the spread of infection while the body’s immune system eliminates the pathogens.

Question 6

What are bactericidal agents?

Answer 6

Bactericidal agents kill and eradicate bacteria.

Question 7

Define chemotherapeutic spectra

Answer 7

The spectrum of a particular drug refers to the species of organism affected by that drug.
e.g., Narrow spectrum, extended spectrum, and broad spectrum

Question 8

What are narrow-spectrum agents?

Answer 8

Agents that act on only single or limited group of microorganism e.g. Isoniazid on Mycobacteria

Question 9

What are extended-spectrum agents?

Answer 9

Agents that affect both gram-positive and gram-negative organisms. e.g., ampicillin

Question 10

What are broad-spectrum agents?

Answer 10

Extended spectrum + Chlamydia + Mycoplasma

e.g., tetracycline and chloramphenicol

Question 11

What is the danger of using broad-spectrum antibiotics?

Answer 11

Administration of broad-spectrum antibiotics can drastically alter the nature of the normal bacterial flora and can precipitate a superinfection of an organism, e.g., candida, whose growth is normally kept in check by the presence of other microorganisms.

Question 12

Requirements for Selection of Antimicrobial Agents

Answer 12

Knowledge of…
a. organism identity and its sensitivity to a particular agent

b. the site of infection

c. the safety of the agents

d. patient factors: immune system, renal dysfunction, hepatic dysfunction, poor perfusion, pregnancy, lactation, and age

e. cost of therapy

Question 13

What is empiric therapy?

Answer 13

It refers to therapy prior to organism identification.

It is used for patients who are acutely ill and require immediate treatment.

Question 14

Can antibiotics cross the blood-brain barrier?

Answer 14

It depends on the antibiotic. The blood-brain barrier ordinarily excludes many antibiotics

Question 15

How are CNS infections treated?

Answer 15

Inflammation enhances penetrability of the BBB and allows sufficient levels of many (but not all) antibiotics to enter the cerebrospinal fluid

Question 16

Why is it important to know the immune status of the patient?

Answer 16

Elimination of infecting organisms from the body depends on an intact immune system.

Immunocompromised patients (weakened immune defenses) require higher than usual doses of bactericidal agents to eliminate the infective organism.

Question 17

Why is knowing renal status important to selecting therapy?

Answer 17

Poor kidney function (10% or less of normal) causes the accumulation of antibiotics that are eliminated by this route, risking ADR.

ADRs can be controlled by adjusting the dose or the dosage schedule.

*The number of functioning nephrons decreases with age, making elderly patients particularly vulnerable

Question 18

Why is knowing hepatic status important to selecting therapy?

Answer 18

Erythromycin and tetracycline concentrate in the liver and are contraindicated in patients with liver disease.

Question 19

Why is pregnancy important to selecting therapy?

Answer 19

a. All antibiotics cross the placenta

b. Adverse effects on the fetus are rare (except for tooth dysplasia and inhibition of bone growth with the tetracyclines)

c. Some anthelmintics are embryotoxic and teratogenic.

Question 20

Is Combination Antimicrobial Therapy advised?

Answer 20

No.

Therapeutically advisable to treat with the single agent that is most specific for the infecting organism.

Question 21

What are the dangers of combination antimicrobial therapy?

Answer 21

a. Emergence of superinfection
b. Occurrence of resistant organisms
c. Antagonism between the drugs
d. Increased incidence of toxicity

Question 22

What is drug resistance?

Answer 22

Bacteria are said to be resistant if their growth is not halted by the maximum level of an antibiotic that is tolerated by the host.

Question 23

How is bacterial resistance spread?

Answer 23

1. By transfer of bacteria between people
2. By transfer of resistance genes between bacteria (usually on plasmids)
3. By transfer of resistance genes between genetic elements within bacteria on transposons (stretches of DNA that can be transported from one plasmid to another, and also from plasmids to chromosomes and vice versa).

Question 24

How do bacteria transfer resistance genes?

Answer 24

By transduction or conjugation

Question 25

What is MRSA?

Answer 25

Methicillin-resistant Staphylococcus aureus is a strain resistant to all antibiotics except vancomycin and possibly ciprofloxacin, rifampin and imipenem/cilastatin

Question 26

Biochemical mechanisms of resistance to antibiotics

Answer 26

1. Production of enzymes that inactivate the drug (e.g. B-lactamases—penicillin; acetyltransferases—chloramphenicol; kinases—aminoglycosides) 2. Alteration of the drug-binding sites, which are binding sites for antibiotics. It occurs with aminoglycosides, erythromycin, and penicillins. 3. Reduction of drug uptake by the bacterium (e.g. tetracyclines) 4. Alteration of enzymes (e.g. dihydrofolate reductase becomes insensitive to trimethoprim)

Question 27

When are prophylactic antibiotics used?

Answer 27

1. Prevention of streptococcal infections in patients with a history of rheumatic heart disease 2. Pretreatment of patients undergoing dental extractions who have implanted prosthetic devices (e.g. artificial heart valves) 3. Prevention of tuberculosis or meningitis among individuals who are in close contact with infected patients 4. Presurgical treatment in gastrointestinal procedures, vaginal hysterectomy, cesarean section, joint replacement, and open fracture surgery

Question 28

Complications of antibiotic therapy

Answer 28

1. Hypersensitivity e.g. the penicillins can cause serious hypersensitivity problems, from rashes (urticaria) to anaphylactic shock 2. Direct toxicity 3. Superinfections

Question 29

What are superinfections?

Answer 29

The overgrowth of opportunistic organisms, especially fungi, which are normally kept in check by normal flora, is called a superinfection. These infections can involve resistant organisms and are often difficult to treat. They can affect the upper respiratory, intestinal, and genitourinary tracts.

Question 30

General mechanism of antimicrobial chemotherapy

Answer 30

1. Inhibition of cell wall synthesis e.g., Penicillin, Cephalosporins, Vancomycin, Bacitracin 2. Inhibition of the function of cellular membrane e.g. Amphotericin B, Colistin, Nystatin, Polymyxin 3. Inhibition of nucleic acid synthesis e.g., Sulphonamide, Trimethoprim, Nalidixic acid, Rifampin 4. Inhibition of protein synthesis e.g., Chloramphenicol, Erythromycin, Tetracycline and Aminoglycosides