ch 12 book (part 2)

Distinguish between drug toxicity

and

allergic reactions to drugs.

A- heightened immunosensitivity, drugs acts as an antigen

T- foreign chemicals harm human tissue

Define the term superinfection, and summarize how it develops in a patient.

A superinfection is a new infection that happens while you're already being treated with antibiotics.
How it happens: Antibiotics kill good bacteria too, so bad ones (like resistant ones or fungi) take over.

broad spectrum

kills many types of microbes (both gram pos and gram neg)

ex: tetracycliners

narrow spectrum

targets specific microbes

ex: polymyxin + some members of penicillin grp

explain the significance of the distinction of broad and narrow spectrum

Broad-spectrum is good when you don’t know the exact cause, but it can kill good bacteria too. Narrow-spectrum is better when you know the cause—it’s safer for your good microbes.

Trace the development of ß-lactam antimicrobials, and identify which microbes they are effective against

ß-lactam antibiotics include penicillins and cephalosporins.

They work against: Mostly Gram-positive bacteria, and some have been modified to work on Gram-negative too.

They stop bacteria from building their cell walls.

Describe the action of ß-lactamases, and explain their importance in drug resistance

ß-lactamases are enzymes made by some bacteria.

They break down ß-lactam antibiotics, making the drugs useless.

Why is it important? It’s a major cause of antibiotic resistance.

List examples of other ß-lactam antibiotics.

• Penicillins 

• Cephalosporins 

• Carbapenems 

• Monobactams 

Describe common cell wall antibiotics that are not in the ß-lactam class of drugs.

• Vancomycin – Inhibits peptidoglycan synthesis (used for Gram-positive bacteria).

• Bacitracin – Blocks transport of peptidoglycan precursors.

• Isoniazid – Targets mycolic acid synthesis in Mycobacterium tuberculosis.

• Ethambutol – Also used against Mycobacterium, affecting cell wall integrity.

The zones of inhibition surrounding the discs in a Kirby-Bauer test are measured and compared with a standard for each drug. The resulting profile of antimicrobial sensitivity is called a(n) _______

antibiogram

antibiogram

A profile of antimicrobial sensitivity based on the results of a Kirby-Bauer test

Why is it important to have a pure culture of the infecting organism for susceptibility testing?

A mixed culture will show variable results as different microbes will have different susceptibilities.

Some drugs interact with sunlight resulting in a skin inflammation called ______

photodermatitis

primary sites of action of antimicrobial drugs in bacteria

• Cell wall

• Nucleic acids

• Cell membrane

• Ribosomes

The formation of benzylpenicilloyl from penicillin may cause ________ reactions.

allergy

alexander Fleming

scientist who first observed the action of penicillin as a product of a fungal contaminant among Staphylococcus colonies

The group of antibiotics originally isolated in the late 1940s from the mold Acremonium are the ______

cephalosporins

true/false: Although cephalosporins are similar to penicillins, most cause fewer allergic responses.

true

An enzyme secreted by certain bacteria that cleaves the beta-lactam ring of penicillin and cephalosporin, and thus provides resistance against the antibiotic, is a(n) ________

beta-lactamase

Aminoglycosides are composed of one or more amino ____ and a(n) ____-carbon ring.

sugars, six

sulfonamides

Synthetic drugs that inhibit folic acid synthesis are in the group

Cephalosporins are ______-spectrum drugs that are ______ to most penicillinases.

broad; resistant

All of the following types of antibiotics inhibit protein synthesis except ______.

rifampicin

Antifungal agents are often toxic to host cells because the fungal and the host cells are both _______ .

eukaryotic

what is eukaryotic again?

a type of cell or organism characterized by having a membrane-bound nucleus and other complex internal structures called organelles

true/false: Fluoroquinolones only inhibit gram-negative bacteria.

False;

Fluoroquinolones are broad spectrum antibiotics which inhibit many Gram-positive bacteria as well.

Quinine is a drug that treat ______ .

malaria

In fungi, a small regulatory _______ binds to a gene and silences it, preventing the synthesis of the target of an antifungal drug. The fungus is temporarily resistant to that drug.

RNA

plasmids called R factors confer ________

antibiotics resistance

The production of β-lactamases is responsible for Blank______.

drug inactivation

Like its relatives zanamivir and oseltamivir, ____ blocks the entry of influenza virus by blocking fusion of the virus with the host cell membrane.

amantadine

The term "postantibiotic era" refers to:

a time when all available antibiotics are no longer useful clinically

Organisms resistant to penicillins and ______ often produce β-lactamases that hydrolyze the β-lactam ring structure of the antibiotic.

cephalosporins

Preparations of live microbes used as a preventive or therapeutic measure to displace or compete with potential pathogens are called ____.

probiotics

probiotics are _______ .

preparations of live microorganisms fed to animals and humans to improve their intestinal biota

Identify the targets of several antibiotics that inhibit protein synthesis.

• Tetracyclines – Bind 30S subunit; block tRNA binding.

• Aminoglycosides (e.g., streptomycin) – Bind 30S; cause misreading of mRNA.

• Macrolides (e.g., erythromycin) – Bind 50S; block translocation.

• Chloramphenicol – Inhibits peptide bond formation at 50S.

• Oxazolidinones – Block formation of the initiation complex at 50S.

Identify the cellular target of quinolones, and provide two examples of these drugs.

Target: DNA gyrase and topoisomerase IV (enzymes needed for DNA replication).

Examples:

• Ciprofloxacin

• Levofloxacin

 Name two drugs that target the cellular membrane.

• Polymyxins (e.g., polymyxin B) – Disrupt Gram-negative bacterial membranes.

• Daptomycin – Targets Gram-positive cell membranes, causing ion leakage.

 Describe the unique problems in treating biofilm infections.

• Biofilms protect microbes with a sticky matrix.

• Bacteria in biofilms grow slower and resist antibiotics.

• They often exchange resistance genes.

• The immune system has difficulty reaching microbes inside biofilms.

Name the four main categories of antifungal agents, and provide one example of each.

• Polyenes –  Amphotericin B

• Azoles –  Fluconazole

• Echinocandins – Caspofungin

• Allylamines – Terbinafine

List two antiprotozoal drugs and three antihelminthic drugs used today.

Antiprotozoals:

• Metronidazole – Used for Giardia, Entamoeba, Trichomonas.

• Chloroquine – Used for Plasmodium (malaria).

Antihelminthics:

• Mebendazole – Inhibits worm microtubules.

• Ivermectin – Paralyzes worms.

• Praziquantel – Disrupts membranes of flatworms and flukes.

Describe three major modes of action of antiviral drugs.

1. Inhibit viral entry – Enfuvirtide for HIV.

2. Inhibit nucleic acid synthesis – Acyclovir for herpes viruses.

3. Inhibit viral assembly/release – Oseltamivir (Tamiflu) for influenza.

 Discuss two possible ways that microbes acquire antimicrobial resistance.

1. Spontaneous mutation – Random DNA changes during replication.

2. Horizontal gene transfer – Bacteria acquire resistance genes via:

   • Conjugation (plasmids)

   • Transformation

   • Transduction (bacteriophages)

List five cellular or structural mechanisms that microbes use to resist antimicrobials.

1. Drug inactivation – ß-lactamases destroy penicillins.

2. Altered target – changes in ribosome structure.

3. Efflux pumps – Pump drug out of cell.

4. Decreased permeability – Altered porins block drug entry.

5. Bypass pathways – Microbe uses alternative enzymes or pathways.

Discuss at least three novel antimicrobial strategies that are under investigation.

• Phage therapy – Using viruses to target specific bacteria.

• CRISPR-based antimicrobials – Editing bacterial DNA to kill or disarm pathogens.

• Quorum sensing inhibitors – Block communication among bacteria, preventing virulence.

hospital environment :

• Hospitals house susceptible patients with weakened defenses
  • Workforce may not strictly adhere to universal precautions
  • This has led to penicillin resistance in nearly 100% of all
  Staphylococcus aureus strains in 30 years

drugs in animal feeds

Nearly 80% of all antibiotics in the United States are given to livestock
• Allegedly decreases infections and improves animal health and
size
• Enteric bacteria share resistance plasmids that are constantly
selected and amplified by exposure to drugs
• These pathogens “jump” to humans and cause drug-resistant
infections

new approaches to antimicrobial therapy

Low-tech solutions:
• Using bacteriophages in Eastern European countries
• Incorporating phage into wound dressings
• Phage are extremely specific and only infect one species of
bacteria, leaving normal microbiota alone

What are probiotics, and why are they important for human health?

Preparations of live microorganisms fed to animals and humans
to improve intestinal biota
• Replace microbes lost during antimicrobial therapy
• Augment the biota already there
• Example: probiotic yogurt
• Safe, effective, useful in treating food allergies

what is Prebiotics?

• Nutrients that encourage the growth of beneficial microbes in
  the intestine
  • Example: fructans encourage the growth of Bifidobacterium in
  the large intestine and discourage the growth of pathogens

what is fecal transplant

Treatment for recurring Clostridioides difficile infections
• Involves transfer of feces, containing beneficial normal biota, from healthy to affected patients via colonoscopy
colonoscopy

major side effects of drug

• Direct damage to tissues through toxicity

• Allergic reactions

• Disruption in the balance of normal microbial biota

toxicity to organ: tetracycline

• Bind to the enamel of teeth, causing a permanent gray to brown
  discoloration
  • Cause liver damage in pregnant women
  • Cross the placenta and are deposited in fetal bones and teeth

toxicity to organ: Diarrhea

Most common complaint associated with oral antimicrobial therapy
• Can progress to severe intestinal irritation or colitis
• Some drugs directly irritate the intestinal lining
• Also caused by disruption of the intestinal microbiota