OIA1015 PRINCIPLES OF ANTIMICROBIAL THERAPY

Antimicrobial Therapy

The use of drugs to treat infections by targeting microorganisms while minimizing harm to the host.

Selective Toxicity

The ability of an antimicrobial to target bacterial structures absent in human cells.

Bacteriostatic Antibiotics

Inhibit bacterial growth and replication, allowing the immune system to eliminate the infection.

Bactericidal Antibiotics

Directly kill bacteria, preferred for severe infections (e.g., sepsis, endocarditis).

Narrow-Spectrum Antibiotics

Target specific bacterial groups (e.g., Penicillin G for Gram-positive bacteria).

Extended-Spectrum Antibiotics

Cover both Gram-positive and some Gram-negative bacteria (e.g., Ampicillin).

Broad-Spectrum Antibiotics

Effective against a wide variety of bacteria (e.g., Tetracyclines, Carbapenems).

Disadvantages of Broad-Spectrum Antibiotics

Disrupt normal flora, leading to superinfections (e.g., C. difficile overgrowth).

Cell Wall Synthesis Inhibitors

β-lactams (Penicillins, Cephalosporins, Carbapenems, Monobactams)

Glycopeptides (Vancomycin)

Protein Synthesis Inhibitors

Aminoglycosides (Gentamicin, Streptomycin) → Bind 30S ribosome.

Macrolides (Erythromycin, Azithromycin) → Bind 50S ribosome.

Nucleic Acid Synthesis Inhibitors

Fluoroquinolones (Ciprofloxacin) → Inhibit DNA gyrase.

Rifampin → Inhibits RNA polymerase.

Folic Acid Synthesis Inhibitors

Sulfonamides, Trimethoprim → Block bacterial folate synthesis.

Cell Membrane Disruptors

Polymyxins (Colistin) → Disrupt Gram-negative bacterial membranes.

Minimum Inhibitory Concentration (MIC)

The lowest drug concentration that inhibits bacterial growth.

Minimum Bactericidal Concentration (MBC)

The lowest drug concentration that kills bacteria.

Concentration-Dependent Killing

Higher concentrations increase bacterial killing rate (e.g., Aminoglycosides, Fluoroquinolones).

Time-Dependent Killing

Killing efficacy depends on the duration the drug remains above MIC (e.g., β-lactams).

Post-Antibiotic Effect (PAE)

Persistent bacterial suppression after drug levels fall below MIC.

Empiric Therapy

Broad-spectrum antibiotic therapy initiated before pathogen identification.

Targeted (Definitive) Therapy

Narrow-spectrum antibiotics based on culture & sensitivity testing.

Factors Affecting Antibiotic Choice

Site of infection, host immune status, renal/hepatic function, pregnancy.

Combination Therapy

Used in severe infections (e.g., tuberculosis, endocarditis) to prevent resistance.

Antibiotic Synergism

Example: β-lactams + aminoglycosides for Enterococcus infections.

Antagonism

Example: Tetracyclines inhibit penicillin’s bactericidal effect.

Intrinsic Resistance

Naturally occurring resistance (e.g., Gram-negative bacteria resist vancomycin).

Acquired Resistance

Mutation or gene transfer mechanisms leading to resistance.

Enzymatic Drug Inactivation

β-lactamases hydrolyze β-lactam antibiotics.

Altered Target Sites

MRSA modifies PBPs, reducing penicillin binding.

Efflux Pumps

Actively remove antibiotics from bacterial cells.

Reduced Drug Uptake

Porin mutations in Gram-negative bacteria prevent antibiotic entry.

Hypersensitivity Reactions

Penicillins & Sulfonamides can cause anaphylaxis.

Superinfections

Broad-spectrum antibiotics disrupt normal flora, leading to C. difficile infections.

Nephrotoxicity

Aminoglycosides, Vancomycin can cause renal damage.

Ototoxicity

Aminoglycosides can cause permanent hearing loss.

Hematologic Toxicity

Chloramphenicol causes aplastic anemia.

β-Lactams (Penicillins, Cephalosporins, Carbapenems)

Used for most Gram-positive & some Gram-negative infections.

Macrolides (Erythromycin, Azithromycin, Clarithromycin)

Alternative for penicillin-allergic patients.

Aminoglycosides (Gentamicin, Amikacin, Streptomycin)

Severe Gram-negative infections (sepsis, pneumonia).

Fluoroquinolones (Ciprofloxacin, Levofloxacin)

UTIs, respiratory infections, bacterial diarrhea.

UTIs, respiratory infections, bacterial diarrhea.

Chlamydia, Rickettsial infections, acne.