INHIBITING THE

GROWTH OF
PATHOGENS IN VIVO
NICO ANGELO C. SOLON, RMT
IN VIVO

• Use of drugs and antibiotics in the treatment of disease inside the body.
SHORT HISTORY

• Alexander Flemming saw Penicillium notatum

moulds grow in his bacterial plate causing a
clearing around the bacteria.
CHARACTERISTIC OF AN IDEAL
ANTIMICROBIAL AGENT

• Kills or inhibits the growth of pathogens.

• Cause no damage to the host.
• Causes no allergic reaction in the host.
• Be stable when stored in solid or liquid form.
• Remain in specific tissues in the body long enough to be effective.
• Kills pathogens before they mutate and become resistant to it.
HOW DO ANTIMICROBIAL AGENTS WORK?

• Inhibits cell wall synthesis

• Damage to cell membranes.
• Inhibition of nucleic acid synthesis.
• Inhibition of protein synthesis.
• Inhibition of enzyme activity.
ANTIBACTERIAL AGENTS

• Antibacterial agents may either be microbicidal or microbiostatic.

• Some antibiotics of antibacterial nature may have antagonist or synergistic properties.
• Different kinds of antibiotics have different modes of actions against bacteria.
MAJOR CATEGORIES IN ANTIBACTERIAL
AGENTS
• Penicillin
• Cephalosporin
• Carbapenem
• Glycopeptides
• Tetracycline
• Aminoglycosides
• Macrolides
• Fluoroquinolones
PENICILLIN
• Aka Beta lactam drugs because of its molecular structure (contains a beta lactam ring).
• Function: inhibits cell wall
• Max effect when: actively dividing
• Natural penicillin: can taken out of nature (Penicillin G and V)
• Effective against:
• Gram positive bacteria
• Some anaerobic bacteria
• Spirochetes
• Gram negative bacteria (Neisseria meningitides, Haemophilus influenza)

• Extended spectrum
• Effective against:
• Gram negative bacilli
CEPHALOSPORIN

• Also beta lactam antibiotics

• Function: also inhibits cell wall
• May be classified as first, second, third, fourth and fifth generation.
• First generation: active against Gram positive bacteria
• Second generation: also active against Gram negative bacteria
• Third generation: more active against Gram negative bacteria (specifically Pseudomonas aeruginosa)
• Fourth generation: Effective against gram positive cocci, MRSA, MRSE and Gram negative bacteria.
CARBAPENEM

• Function: targets the cell envelope and has excellent activity against broad spectrum of bacteria.
• Potent against: aerobic Gram positive bacteria, most aerobic Gram positive bacteria and most
anaerobes.
• Example: Imipenem
GLYCOPEPTIDES

• Function: targets the cell envelope

• Potent against: anaerobic Gram positive bacteria
• Contains toxic side effects
• Example: Vancomycin
TETRACYCLINE

• Broad spectrum, bacteriostatic drugs

• Function: targets bacterial ribosomes.
• Effective against:
• Chlamydia
• Mycoplasma
• Rickettsia
• Vibrio cholerae,
• Spirochetes
• Borellia spp.
AMINOGLYCOSIDES

• Bactericidal broad spectrum drugs

• Function: inhibits bacterial protein synthesis
• Effective against:
• Aerobic Gram negative bacteria
• Enterobactericieae
• E. coli
• Klebsiella
• Proteus
• Serratia
• Yersinia
• P. aeruginosa
• Vibrio cholerae
• Ineffective against: anaerobes
MACROLIDES

• Bacteriostatic at lower doses and bactericidal in higher doses.

• Function: inhibits protein synthesis
• Examples:
• Erythromycin
• Clarithromycin
• Azithromycin
• Effective against:
• Chlamydia
• Mycoplasma
• T. pallidum
• Legionella spp.
FLUOROQUINOLONES

• Bactericidal drugs that inhibit DNA synthesis.

• Example: Ciprofloxacin
• Effective against:
• Enterobacteriaceae
• P. aeruginosa
MULTIDRUG THERAPY

• Commonly used against tuberculosis.

• Mycobacterium tuberculosis medications (RIPE)
• Rifampin
• Isoniazid
• Pyrazinamide
• Ethambutol
ANTIFUNGAL AGENTS
• The challenge in antifungal agents arise from the
eukaryotic nature of fungus as opposed to
bacteria.
• Some drugs tend to be more toxic to the patient.
• Antifungal agents work by:
• Binding to cell membrane sterols (nystatin and
amphotericin B)
• Interfering sterol synthesis (clotrimazole and
miconazole)
• Blocking mitosis or nucleic acid synthesis
(griseofulvin and 5-flucytosine)
ANTIPROTOZOAL AGENTS

• Works by:
• Interfering the DNA and RNA synthesis
• Interfering by protozoal metabolism
• Examples: Metronidazole
ANTIVIRAL AGENTS
SUPERBUGS

• Multidrug resistant organisms.

• Examples:
• Methicillin Resistant Staphylococcus aureus
• S. pyogenes
• Vancomycin Resistant Enterococcus
• Pseudomonas aerigunosa
• Clostridium difficile
DRUG RESISTANCE MECHANISM

• Intrinsic resistance (naturally resistant against drugs)

• Acquired resistance
• Chromosomal mutation in the structure of the drug binding site
• Chromosomal mutation in the cell’s permeability
• Acquisition of gene carrying the enzyme that inactivates the drug
• Acquisition of a gene to create a multidrug resistant pump
• Production of B-lactamase (penicillinase and cephalosporinase) against penicillin and celphalosporin.
FACTORS TO BE CONSIDERED IN
ADMINISTERING ANTIBIOTICS
• Susceptibility
• Allergies
• Age
• Pregnancy
• Site of infection
• Other medication being received
• Medical history
• Immune system status
ANTIBIOTIC SENSITIVITY TESTING

• The method of testing antibiotic sensitivity

• Uses a specialized culture medium known as the
Mueller Hinton Agar
KIRBY-BAUER METHOD

• Small wafers containing antibiotics are placed

onto a plate upon which bacteria are growing. If
the bacteria are sensitive to the antibiotic, a
clear ring, or zone of inhibition, is seen around
the wafer indicating poor growth
• Reporting is either: Sensitive, Intermediary or
Resistant