Quiz 1 - Principles of Antibacterial Chemotherapy

Chemotherapy

Use of a chemical substance to treat various aspects of disease.

Anti-infective agents

Agents used to kill an infectious agent or inhibit its spread.

Anthelmintics

are medicines that kill worms (helminths) or paralyze them so the body can remove them through stool.

Antiprotozoals

are medicines that kill protozoa, which are single-celled parasites.

Antimicrobial agents

Special group of chemotherapeutic agents used to treat diseases caused by microbes

Synthetic Drug
Semi-synthetic Drug
Antibiotics

Origin / Source

Synthetic Drugs

Completely manufactured in the laboratory.

Semi-synthetic Drugs

Natural antibiotics that are chemically modified.

Antibiotics

A substance produced by a microorganism that in small amounts inhibits another microorganism

Bacteria
Viruses
Fungi
Protozoans
Helminths

SUSCEPTIBLE ORGANISMS

Narrow Spectrum
Intermediate Spectrum
Broad Spectrum
Broad-spectrum Antibiotics

SPECTRUM OF ACTIVITY

Narrow Spectrum

Active against only a few organisms

Intermediate Spectrum

Active against more organisms than narrow-spectrum agents.

Broad Spectrum

Active against many Gram-positive and Gram-negative bacteria.

Broad-spectrum Antibiotics

Advantage

• Useful for empiric therapy.

Disadvantages

• May destroy normal flora.

• May cause superinfection by opportunistic pathogens.

• May contribute to antimicrobial resistance.

Bactericidal
Bacteriostatic

EFFECT

Bactericidal

Kills microorganisms

Bacteriostatic

Inhibits bacterial growth, allowing the host immune system to eliminate the microorganisms

Minimum Inhibitory Concentration (MIC)

Concentration that inhibits visible bacterial growth after 24 hours under specified conditions

Minimum Bactericidal Concentration (MBC)

Concentration that results in a 1,000-fold reduction in bacterial density after 24 hours.

Bactericidal + Bactericidal

Usually synergistic (working together equals a big sum of their individual effect)

Bacteriostatic + Bacteriostatic

Usually additive.

Bacteriostatic + Bactericidal

May be antagonistic because bactericidal drugs work best on actively growing bacteria

Cell Wall Synthesis
Protein Synthesis
Cell Membrane Disruptors
Nucleic Acid Synthesis
Antimetabolites

five major mechanisms of antibacterial drugs

Cell Wall Synthesis Inhibitors (Breaking the wall)

Beta-lactam Antibiotics

• Penicillins

• Cephalosporins

• Carbapenems

• Monobactams

Polypeptide Antibiotics

• Bacitracin

• Vancomycin

Antimycobacterials

• Isoniazid

• Ethambutol

Protein Synthesis Inhibitors (Stop making protein)

Target the 30S or 50S ribosomal subunit, allowing selective toxicity because bacterial ribosomes differ from human ribosomes.

Aminoglycosides

• Streptomycin

• Gentamicin

• Neomycin

• Tobramycin

• Amikacin

• Kanamycin

• Netilmicin

• Sisomicin

Tetracyclines

• Tetracycline

• Oxytetracycline

• Chlortetracycline

• Methacycline

• Demeclocycline

• Doxycycline

• Minocycline

Glycylcyclines

• Tigecycline

Macrolides

• Erythromycin

• Clarithromycin

• Azithromycin

• Telithromycin

Lincosamides

• Clindamycin

Streptogramins

• Dalfopristin

• Quinupristin

Oxazolidinones

• Linezolid

Chloramphenicol Pleuromutilins

• Retapamulin

Cell Membrane Disruptors (Punching the cell membrane)

Bind to phospholipids of the bacterial cell membrane.

Polymyxins

• Polymyxin B

• Colistin

Lipopeptides

• Daptomycin

Nucleic Acid Synthesis Inhibitors

Some agents possess increased affinity for prokaryotic enzymes.

Rifamycins

• Rifampicin

Quinolones

• Nalidixic Acid

• Norfloxacin

• Ciprofloxacin

• Ofloxacin

• Levofloxacin

• Gatifloxacin

Antimetabolites (Starving the bacteria)

Interfere with folic acid synthesis.

Sulfonamides

• Sulfasalazine

• Sulfamethoxazole

• Sulfadiazine

• Sulfadoxine

Trimethoprim

Empiric Therapy
Definitive Therapy

NATURE OF THE MICROORGANISM

Empiric Therapy

Treatment started before the exact microorganism is identified.

Usually uses broad-spectrum antibiotics because the causative organism is still unknown.

Definitive Therapy

Treatment started after the microorganism has been identified by laboratory testing.

Uses a narrow-spectrum antibiotic whenever possible.

Antibiogram

is a laboratory report showing the susceptibility of bacteria to different antimicrobial agents

Age
Immune system
Renal function
Hepatic function
Lactation and pregnancy
Perfusion

PATIENT FACTORS

Toxicity

Allergic reactions

Side effects

Drug interactions

SAFETY OF THE AGENT

Hypersensitivity

Allergic reactions ranging from mild rash to severe anaphylaxis

Idiosyncratic Reaction

An unusual or unpredictable reaction that occurs in only a few individuals.

Toxicity Reactions

Damage to organs such as:

Kidney (nephrotoxicity)

Liver (hepatotoxicity)

Ear (ototoxicity)

ANTIMICROBIAL RESISTANCE

develops when microorganisms are no longer affected by drugs that previously killed or inhibited them.

Common Causes

• Overuse of antibiotics

• Misuse of antibiotics

• Incomplete antibiotic therapy

• Self-medication

• Unnecessary antibiotic prescriptions

• Incorrect dose or duration

• Use of broad-spectrum antibiotics when unnecessary

Consequences

• Treatment failure

• Longer hospital stay

• Increased healthcare costs

• More severe infections

• Spread of resistant microorganisms