M5: Antimicrobial Agents in Therapy; Bacteria and Disease

Antimicrobial Agent

collectively referred to as chemotherapeutic agent used to treat infectious diseases.

any chemical drug used to treat an infectious disease.

antimicrobial chemotherapy

the use of chemotherapeutic drugs to control infection

Chemotherapy

coined by PAUL EHRLICH, a German medical Researcher

describes those chemical agents that kill pathogen without injuring the host.

a. Antibacterial

b. Antifungal

c. Antiprotozoal

d. Antiviral

e. Antihelminthic

Types of Agents

antibacterial

designed to fight against or kill bacteria

antifungal

fungal infections

Local Antifungal agents: administered topically

systematic Antifungal agents: administered orally or intravenously

butocanazole

clotrimazole

econzole

fenticonazole

isocanazole

ketocanazole

Local Antifungal Agents

antifungal agents that is administered topically.

Systematic Antifungal Agent

antifungal agents administered orally or intravenously.

antiprotozoal

destroys protozoa; for protozoal diseases

eflorithine
furzolidine
hydroxychloroquine
melarsoprol
metronidazole

antiviral

for viral diseases

abacavir for HIV

acyclovir for herpes

adefovir for hepa b

amantadine for influenza

ampligen

tamiflu for influenza type A

Antihelminthic

albendazole

mebendazole

thiabendazole

fenbendazole

Antibiotic

selective poison: kills desired bacteria, but not the cells.

each type of antibiotic affects different bacteria in different ways

include synthetic antibacterial agents: sulfonamides and quinolones

sulfonamides
quinolones

synthetic antibacterial agents under antibiotics

sulfonamides

Antibiotics that stop bacteria from making folic acid, a vitamin they need to grow.

Used to treat infections like urinary and respiratory tract infections.

quinolones

Antibiotics that interfere with bacteria's ability to multiply by messing up their DNA.

Used to treat urinary and respiratory tract infections, as well as skin and gastrointestinal infections.

folic acid

a vitamin that bacteria needs in order to grow

bacteria
fungi
actinomycetes

substances produced by various species of microorganisms

actinomycetes

suppress the growth of other microorganisms and to destroy them

a. some species of fungi (penicillum and cephalosphorium)

b. species of actenomycetes (gram+ filamentous bacteria)--streptomyces

c. bacillus (gram+ spore formers)

d. myxobacteria (gram- bacteria)

e. plants, herbs, fish

Where do antibiotics come from?

selective toxicity

Ability of a drug to target specific organisms or cells while leaving others unharmed.

Prokaryotes (bacteria) are the most distinct.

Fungi and protozoa are more closely related to humans.

Viruses rely on host cell machinery.

Cancer cells are derived from our own cells.

dates back to the EGYPTIANS who used moldy bread to treat SURFACE INFECTION

History of Antimicrobial Therapy:

FIRST antimicrobial

Paul Ehrlich (20th century)

differential staining of tissue, bacteria

developed SALVARSAN - used against syphilis

search for magic bullet that would attack bacterial structures only, not ours.

salvarsan

used against syphilis

Alexander Fleming

discovered Penicillin in 1929

noticed that the growth of staphylococcus aureus was inhibited in presence of the mold produced by Penicillium Fungi

Antibiotics

produced by organisms that have inhibitory effects on other organisms,

ex: penicillin, streptomycin

synthetic drugs

produced in lab

ex: salvarsan, sulfa drugs

a. Broad Spectrum
b. Narrow Spectrum

Classification of Antibiotics according to Spectrum

Broad Spectrum

Effective against a wide range of bacteria.

Prevents synthesis of Glycopeptides' enzyme that forms cross-links between peptidoglycan polymers in cell walls.

Example: penicillin.

Narrow Spectrum

Effective against a limited/narrow range of bacteria.

Prevents bacterial resistance from occurring.

a. Bactericidal
b. Bacteriostatic

Classification of Antibiotics according to Antimicrobial Activity

bacteriosidal

Directly kills the bacteria.

Choice of antibiotic depends on location and severity of infection.

Example: Central Nervous System (CNS) infection requires bactericidal treatment.

Bacteriostatic

Inhibits the growth of bacteria.

Keeps the invader in check.

Host immune system is responsible for killing the bacteria.

a. Locally Acting - topical agent

b. Systemically - acting affects several body systems (IV route)

Classification of Antibiotics according to Absorbability of Site of Administration

a. agents that disrupt the cell membrane (anti-fungal drugs)

b. agents that change permeability of cell membrane ( azoles, clotrimoxazole, ketoconazole)

Classification of Antibiotics according to Mechanism of Action

Aminoglycosides

refers to streptomycin, gentamycin, and kanamycin

semi-synthetic antibiotics
synthetic antibiotics
natural antibiotics

classification based on source of antibacterial agents

semi-synthetic antibiotics

produced by microbes that are subsequently modified by organic chemist to increase antimicrobial properties.

-ampicillin

-amikacin

synthetic antibiotic

man made in lab

1st synthetic antibiotic was SALVARSAN, now called arsphenamine (by Paul Ehrlich)

- sulphonamides

- contrimoxazole

- quinolones

Natural Antibiotic

not made of synthetic material

produced naturally

-garlic

a. Inhibit DNA Replication

b. Inhibit the Synthesis of Folic Acid

c. Inhibits RNA Synthesis

antibiotics act on nucleic acid

Antimicrobial Resistance (AMR)

Acquired ability of microorganisms to resist chemotherapeutic agents. (drug resistance)

Happens when bacteria, viruses, fungi, or parasites stop responding to medicines.

Occurs due to genetic changes.

Can spread between people and animals, including through food of animal origin.

acquired resitance

when a particular microbe obtains the ability to resist a particular antimicrobial agent to which it was previously susceptible.

multidrug-resistant (MDR)

resistant to at least one antibiotic in three or more drug classes.

Superbugs

bacteria with resistance to several commonly used antibiotics

combination therapy

treatment involving one or more drug

rationale: lesser likelihood that pathogen develops resistance to multiple drugs.

Empirical Diagnosis and/or treatment

diagnosis or treatment based on clinical educated guesses in the absence of complete or perfect information.

a. Natural Occurrence
b. Self-Medication
c. Clinical Misuse
d. Environmental Pollution
e. Livestock
f. Pesticides

Causes of Antimicrobial Resistance (AMR)

Natural Occurrence

able to adapt to their environment, survive, and continue to produce offspring.

Self-Medication

taking medicines on one's own initiative or on another person's suggestion, who is not a "certified medical professional."

clinical misuse

prescribed antibiotics were unnecessary
duration of therapy was incorrect

environmental pollution

inappropriate disposal of unused/expired medication, exposes microbes in environment to antibiotics, which trigger evolution of resistance.

livestock

antibiotics are fed to livestock to act as growth supplements and preventative measure to decrease infections.

results in transfer of resistant bacterial strains into the food that humans eat, causing potentially fatal transfer of disease.

Pepticides

overuse results in many of these microbes evolving a tolerance against these antimicrobial agents.

Susceptibility

Microorganisms are sensitive to antimicrobial agents and can be killed or inhibited by them.

Resistance

Microorganisms have developed the ability to withstand the effects of antimicrobial agents and are no longer easily killed or inhibited by them.

a. Inhibition of cell wall
b. disruption of cell membrane function
c. inhibition of protein synthesis
d. action as antimetabolites
e. inhibition of nucleic acid synthesis

Mode of Action or mechanism of antimicrobial drugs

Disease

An abnormal state in which part or all of the body is not properly adjusted or unable to carry out usual functions.

Any deviation from one's current condition of health.

Result of undesirable relationship between host and pathogen.

Interruption in the normal functioning of the body or its part.

Infection

Pathogenic microorganisms invading the body.

Symbiosis

Relation between the indigenous flora and the host.

Commensalism

Type of symbiosis in which one organism benefits from the other without harming it.

Mutualism

Form of symbiosis in which both organisms benefit from the relationship.

Parasitism

Connection in which one organism benefits from another while also harming it.

Pathogen

Organism that invades and causes damage or injury to the host.

Pathogenicity

Refers to an organism's ability to cause disease.

Pollution

Refers to the presence of undesirable substances in water, air, or soil.

Contamination

Presence of harmful organisms outside of their normal environment, like bacteria in food.

Koch's Postulate

Released in 1980, four criteria designed to determine if a certain organism is the cause of a certain disease.

formulated by Robert Koch & Friedrich Loeffer in 1884, based on earlier concepts describes by Jakob Henle.

1. The organism must always be present in every case of the disease.

2. the organism must be isolated from a host containing the disease and grown in pure culture.

3. samples of the organism taken from pure culture must cause the same disease when inoculated into a healthy animal in the laboratory.

4. the organism must be isolated from the inoculated animal and must be identified as the same original that was first isolated from the originally diseased host.

Four Criteria of Koch's Postulates

1. portal of entry
2. virulence of microorganisms
3. number of microbes
4. defensive powers of the host

Factors that Influence Occurrence of Infection

portal of entry

organism may fail to produce disease when introduced into some other route/pathway

virulence of microorganisms

ability of microbes to produce disease by overcoming defensive power of host

number of microbes

abundant

small number of microorganisms

defensive power of the host

antibacterial factors that destroy or inhibit growth of microorganisms

refers to the body's immune system, such as the first line of defense

Microbial Growth

refers to an increase in number of cells rather than an increase in cell size; likelihood of disease increases as number of pathogens increase

Microbial Antagonism

one microbe or group of microbes wards off another

Mechanical

Chemical

Toxin

Immunologic

How Organisms Produce Disease

Mechanical

organisms directly damage tissues or surface.

ex: warts, leprosy

Chemical

refers to leukocidins and coagulase

Leukocidins

destroys WBC (escapes phagocytosis)

disruption of phagocytosis promotes survival in mouse model of infection

phagocytosis

process by which certain living cells called phagocytes ingest or engulf other cells or particles.

mouse model of infection

enable the characterization of host immune factors that protect against or promote virus infection

Coagulase

coagulates fibrinogen of blood.

bacteria form a fibrin clot around themselves, protecting them from host immune system.

mostly in gram+ bacteria.

fibrinogen

plasma protein that is converted to fibrin in the clotting process

fibrin

protein that forms the basis of a blood clot

toxin

refers to exotoxin and endotoxin.

Exotoxin

inside a gram+ bacteria as metabolic product of growing cell

are toxic substances secreted by bacteria and released outside the cell.

a. Neurotoxin
b. Enterotoxin
c. Cytotoxin

three types of exotoxins

neurotoxin

interferes in the nerve impulse transmission

enterotoxin

affects cell lining of GI Tract

Cytotoxin

kills host cells, affect their function

Endotoxin

outer membrane of gram- bacteria.

outer membrane of cell wall.

Immunologic

consequence of immune response of the host to microorganism.

ex: damage to liver⟶Hepatitis Complement

Complement System

systems of plasma proteins that can be activated directly or indirectly by pathogen-bound antibody.

a. Activation of Inflammation

b. opsonization (labeling) of pathogens and cells for clearance/destruction.

c. direct killing of target cells/microbes by lysis

Functions of Complement System

opsonization

labeling of pathogens

an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes.

lysis

destruction of target cells or microbes

the breakdown of a cell caused by damage to its plasma (outer) membrane.

a. affects cells function, GIT

b. No fever

Diphtheria

Botulism

Tetanus

effects in the body: Gram+ Exotoxin

a. fever

b. weakness

c. aches

d. shock

Meninggococcal

Meningitis

UTI

effects in the body: Gram- Edotoxin

infection

Contamination or invasion of body tissue by pathogenic organisms

1. Communicable
2. Non-Communicable

classification of infection: based on Manner Causative Agent Reaches the Host