Antimicrobial Agents and Chemotherapy

Controlling Microbial Growth In-Vivo

• Focuses on using antimicrobial agents
• Objectives are to learn the different ways that microbial growth can be controlled or inhibited in vitro, understand microbial growth curves and learn different ways of culturing microorganisms.
• Antibiotic Sensitivity Assay helps in finding the most appropriate antibiotic to treat a bacterial infection.

Chemotherapy

• Involves using chemicals (drugs) to treat diseases or conditions.
• Chemotherapeutic agents are drugs used for this purpose.
• Antimicrobial agents are substances used to treat infectious diseases in vivo through inhibition or killing.
• Some antimicrobial agents are antibiotics.
• Antimicrobial agents can be antibacterial, anti fungal, antiprotozoal or antiviral
• Antibiotics are substances produced by microorganisms that inhibit other groups of microorganisms.

The First Antibiotic Discovered

• The first antibiotic was discovered by Fleming in 1928
• From this the modern Streak Culture experiment was founded

Ideal Antimicrobial Agent

• Should kill or inhibit pathogens.
• Should not cause damage or an allergic reaction to the host.
• Should be stable when stored (in liquid or solid form).
• Should remain in specific tissues long enough to take effect.
• Should kill the pathogen quickly to prevent it from mutating or becoming resistant.

How Antibiotics Work

• Inhibiting cell wall synthesis
• Damaging the cell membrane
• Inhibiting RNA or DNA synthesis
• Inhibiting protein synthesis
• Inhibiting enzyme activity
• Bacteriostatic antibiotics inhibit growth
• Bactericidal antibiotics kill

Types of Antibiotics

• Narrow-spectrum antibiotics target certain groups only like colistin and nalidixic acid killing gram (-) bacteria only.
• Broad-spectrum antibiotics kill many types of bacteria like ampicillin, chloramphenicol and tetracycline killing both gram (-) and gram (+) bacteria.
• Multidrug Therapy (MDT) involves using two or more drugs simultaneously, such as in the treatment of tuberculosis, when one drug isn't enough.

Major Categories of Antibacterial Agents

• Penicillins are bactericidal and interfere with cell wall synthesis
• Cephalosporins are bactericidal and interfere with cell wall synthesis
• Tetracyclines are bacteriostatic and inhibit protein synthesis
• Aminoglycosides are bactericidal and inhibit protein synthesis
• Macrolides are bacteriostatic at lower doses, and bactericidal at higher doses, they inhibit protein synthesis
• Fluoroquinolones are bactericidal and inhibit DNA synthesis

Synergism vs Antagonism

• Synergism involves using two antimicrobial agents together to produce a greater degree of pathogen killing than either drug alone.
• Antagonism occurs when two drugs work against each other, resulting in a lesser extent of pathogen killing than either drug alone.

Antifungal Agents

• Most antifungal agents work by binding with cell membrane sterols, disrupting sterol synthesis or blocking mitosis or nucleic acid synthesis.
• Antifungal and antiprotozoal agents tend to be more toxic to the patient because they are eukaryotic organisms.

Antiprotozoal Agents

• They are usually toxic to the host.
• They work by interfering with DNA and RNA synthesis or interfering with protozoal metabolism.

Antiviral Agents

• Are the newest weapons in antimicrobial methodology.
• They are difficult to develop because viruses are produced within host cells.
• Some drugs are effective only in certain viral infections, working by inhibiting viral replication within cells.
• Antiviral agent cocktails (several drugs administered simultaneously) are used to treat HIV infection.

Drug Resistance

• Superbugs are microbes (mainly bacteria) that have become resistant to one or more antimicrobial agents.
• Bacterial superbugs include methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE) and multidrug-resistant Mycobacterium tuberculosis (MDR TB) and strains of Acinetobacter, Burkholderia, E. coli, Klebsiella, Pseudomonas, Stenotrophomonas, Salmonella, Shigella, and N. gonorrhoeae
• Other bacterial superbugs also include β-lactamase-producing strains of Streptococcus pneumoniae and Haemophilus influenzae, and carbapenemase-producing Klebsiella pneumoniae.

How Pathogens Become Drug Resistant

• Intrinsic resistance is natural resistance, due to lack of specific target site for the drug to bind or the drug is unable to cross the organism’s cell wall (CW) or cell membrane (CM)
• Acquired resistance occurs when bacteria that were once susceptible to a particular drug become resistant
• Plasmids can carry multiple antibiotic resistance genes called resistance factor (R-factor).

Fighting Drug Resistance

• Education of healthcare professionals and patients is key
• Patients should stop demanding unnecessary antibiotics.
• Physicians should avoid being pressured by patients and should prescribe drugs only when warranted.
• Clinicians should prescribe a narrow-spectrum drug if lab results indicate it will be effective.
• Patients should safely dispose of excess or outdated medications.
• Antibiotics should not be used in a prophylactic manner.
• Healthcare professionals should practice good infection control.
• Patients should take drugs in the manner prescribed.

Empiric Therapy

• It is when drug therapy is initiated before laboratory results are available.
• It is sometimes necessary to save a patient's life.
• Clinicians make an "educated guess" based on past experience with the type of infectious disease and the most effective drugs.
• Factors to consider include whether the pathogen identity is known, patient allergies, age, pregnancy status, formulary restrictions, site of the infection, other medications the patient is taking, other medical problems, whether the patient is leukopenic or immunocompromised and the cost of the drug(s).

Pocket Chart

• A pocket chart can be used for aerobic Gram-negative bacteria
• It is a quick reference whenever empiric therapy is necessary.

Undesirable Effects of Antimicrobial Agents

• Organisms susceptible to the agent will die, but resistant ones will survive; this is known as selecting for resistant organisms.
• The patient may become allergic to the agent.
• Many agents are toxic to humans, some very toxic.
• Prolonged use of a broad-spectrum antibiotic may destroys the normal flora, resulting in an overgrowth of bacteria known as a superinfection.

ESKAPE Pathogens

• Enterobacter species cause opportunistic infections in hospitalized patients
• Enterococcus faecium is hospital-acquired .
• Staphylococcus aureus is normal flora of the human body.
• Klebsiella pneumoniae are pathogens of the lower respiratory tract
• Acinetobacter baumannii is nosocomial and cause opportunistic infections
• Pseudomonas aeruginosa is found in hospital settings and are oppotunistic pathogens in immunocompromised patients