Antimicrobial Chemotherapy Flashcards
What are antimicrobial drugs?
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.
What is the principle of selective antimicrobial therapy?
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.
Ideal properties of an antimicrobial agent
- Selective, broad spectrum, and bactericidal
- Non-toxic to host
- Long plasma half-life (fewer doses)
- Good tissue distribution
- Low plasma-protein binding
- No interference with other drugs
Classification of antibacterials
- Chemical. e.g., Tetracycline and Aminoglycosides
- 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
What are bacteriostatic drugs?
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.
What are bactericidal agents?
Bactericidal agents kill and eradicate bacteria.
Define chemotherapeutic spectra
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
What are narrow-spectrum agents?
Agents that act on only single or limited group of microorganism e.g. Isoniazid on Mycobacteria
What are extended-spectrum agents?
Agents that affect both gram-positive and gram-negative organisms. e.g., ampicillin
What are broad-spectrum agents?
Extended spectrum + Chlamydia + Mycoplasma
e.g., tetracycline and chloramphenicol
What is the danger of using broad-spectrum antibiotics?
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.
Requirements for Selection of Antimicrobial Agents
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
What is empiric therapy?
It refers to therapy prior to organism identification.
It is used for patients who are acutely ill and require immediate treatment.
Can antibiotics cross the blood-brain barrier?
It depends on the antibiotic. The blood-brain barrier ordinarily excludes many antibiotics
How are CNS infections treated?
Inflammation enhances penetrability of the BBB and allows sufficient levels of many (but not all) antibiotics to enter the cerebrospinal fluid
Why is it important to know the immune status of the patient?
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.
Why is knowing renal status important to selecting therapy?
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
Why is knowing hepatic status important to selecting therapy?
Erythromycin and tetracycline concentrate in the liver and are contraindicated in patients with liver disease.
Why is pregnancy important to selecting therapy?
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.
Is Combination Antimicrobial Therapy advised?
No.
Therapeutically advisable to treat with the single agent that is most specific for the infecting organism.
What are the dangers of combination antimicrobial therapy?
a. Emergence of superinfection
b. Occurrence of resistant organisms
c. Antagonism between the drugs
d. Increased incidence of toxicity
What is drug resistance?
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.
How is bacterial resistance spread?
- By transfer of bacteria between people
- By transfer of resistance genes between bacteria (usually on plasmids)
- 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).
How do bacteria transfer resistance genes?
By transduction or conjugation
What is MRSA?
Methicillin-resistant Staphylococcus aureus is a strain resistant to all antibiotics except vancomycin and possibly ciprofloxacin, rifampin and imipenem/cilastatin
Biochemical mechanisms of resistance to antibiotics
- Production of enzymes that inactivate the drug (e.g. B-lactamases—penicillin; acetyltransferases—chloramphenicol; kinases—aminoglycosides)
- Alteration of the drug-binding sites, which are binding sites for antibiotics. It occurs with aminoglycosides, erythromycin, and penicillins.
- Reduction of drug uptake by the bacterium (e.g. tetracyclines)
- Alteration of enzymes (e.g. dihydrofolate reductase becomes insensitive to trimethoprim)
When are prophylactic antibiotics used?
- Prevention of streptococcal infections in patients with a history of rheumatic heart disease
- Pretreatment of patients undergoing dental extractions who have implanted prosthetic devices (e.g. artificial heart valves)
- Prevention of tuberculosis or meningitis among individuals who are in close contact with infected patients
- Presurgical treatment in gastrointestinal procedures, vaginal hysterectomy, cesarean section, joint replacement, and open fracture surgery
Complications of antibiotic therapy
- Hypersensitivity e.g. the penicillins can cause serious hypersensitivity problems, from rashes (urticaria) to anaphylactic shock
- Direct toxicity
- Superinfections
What are superinfections?
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.
General mechanism of antimicrobial chemotherapy
- Inhibition of cell wall synthesis e.g., Penicillin, Cephalosporins, Vancomycin, Bacitracin
- Inhibition of the function of cellular membrane e.g. Amphotericin B, Colistin, Nystatin, Polymyxin
- Inhibition of nucleic acid synthesis e.g., Sulphonamide, Trimethoprim, Nalidixic acid, Rifampin
- Inhibition of protein synthesis e.g., Chloramphenicol, Erythromycin, Tetracycline and Aminoglycosides
