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Define antimicrobial drugs.
therapeutic compounds that kill microbes or inhibit their growth
Who discovered penicillin?
Alexander Fleming
Broad-spectrum vs Narrow-spectrum drugs
o Broad-spectrum drugs: effective against both Gram-negative and Gram-positive bacterial cells
o Narrow-spectrum drugs: target a limited range of bacteria
What is empiric therapy?
treatment based on clinical presentation in the absence of definitive or complete clinical data
Prolonged treatment with broad-spectrum antimicrobial drugs can disrupt our normal microbiota. What infection are hospitalized patients at risk for due to prolonged use of broad-spectrum antimicrobial drugs?
Clostridioides difficile
Bacteriostatic vs Bactericidal antimicrobial drugs
o Bacteriostatic antimicrobial drugs: prevent bacteria from growing
o Bactericidal antimicrobial drugs: actively kill bacteria
What is a serious drawback that can occur when using a bactericidal drug for an endotoxin-producing Gram-negative bacterial infection?
- while targeting the pathogen they also tend to kill off normal microbiota
- can also lead to a spike in bacterial toxin release that can be deadly
Antibiotic vs Synthetic antimicrobial vs Semisynthetic antimicrobial
o Antibiotics: naturally occurring antimicrobial compounds
o Synthetic antimicrobials: wholly manufactured by chemical processes
o Semisynthetic antimicrobials: naturally occurring antibiotics that can be chemically modified to improve their pharmacological actions and/or stability
Drugs that have been modified from their core molecule are denoted by "generations". Which of the following would be the oldest generation drug? Which would be the newest generation drug? Which would have the most expanded capabilities over their predecessors?
1st generation --> oldest
4th generation --> newest; most expanded capabilities
Define the selective toxicity of a drug
drug inhibits or kills the targeted microbe without damaging host cells
What is the therapeutic index of a drug?
the ratio of the maximum tolerated or safe dose to the minimum effective or therapeutic dose
T or F: A drug with a high therapeutic index is safer than a drug with a narrow therapeutic index.
True
Because the kidneys and liver are key organs that metabolize and eliminate drugs, they may be particularly susceptible to damage by certain drugs. What is the general name for a drug that is toxic to the kidneys? What is the general name for a drug that is toxic to the liver?
kidneys --> nephrotoxic
liver --> hepatotoxic
When talking about drugs, what is half-life?
the time it takes for half of a dose to be eliminated or deactivated by the body
What superfamily of drugs work by blocking cell wall synthesis? What molecule do most bacterial cell walls consist of?
Beta-lactam antimicrobials; peptidoglycan
What is the function of beta-lactamases?
Inactivate beta-lactam drugs
How do beta-lactamase inhibitors such as clavulanate work?
- have a beta-lactam ring structure and bind strongly to beta-lactamase enzymes.
- this binding blocks beta-lactamase from deactivating the administered antimicrobial
Which generation of cephalosporin is used to combat MRSA/ORSA strains?
Fifth generation
What drug family is effective against a variety of multidrug-resistant (MDR) bacterial strains, so they are often reserved to fight strains that are healthcare-acquired?
Carbapenems
What does the abbreviation CRE stand for?
Carbapenem-resistant Enterobacterales
What does the abbreviation CRA stand for?
Carbapenem-resistant Acinetobacter
What drug family is not a beta-lactam, but inhibits cell wall synthesis?
Glycopeptides
What is the name of the glycopeptide drug used to treat MRSA and Clostridioides difficile infections?
Vancomycin
What antibiotic is the Staphylococcus aureus strain VRSA resistant to?
Vancomycin
What does the drug isoniazid target?
mycolic acid construction in cell walls of acid-fast bacteria
What molecule is targeted by quinolones and rifamycins?
Quinolones target DNA replication enzymes (DNA gyrase & topoisomerases); rifamycins targets RNA polymerase
What drug family targets folic acid synthesis?
Sulfa drugs (sulfonamides)
Why are human cells not affected by sulfonamide drugs?
mammals do not make their own folic acid and therefore do not have the enzyme that these drugs target
What is drug synergism?
the combined effectiveness of two drugs that's greater than the sum of their effectiveness when used alone
Why is it more difficult to develop drugs that target viruses and eukaryotes?
Inflicts collateral damage on our cells
What category of antiviral drugs stimulate an immune response to viruses?
interferons
When are antiviral drugs most effective?
when viruses are actively replicating
Name two structures that most antifungal drugs target
fungal cell walls and plasma membranes
Azoles, allylamines, and polyenes target fungal plasma membranes. What molecule are they specifically targeting?
Fungal plasma membranes
What type of microbe causes athlete’s foot and ringworm?
Fungus
What do antifungal echinocandin drugs target?
an enzyme that makes beta-glucan (β-glucan), a component of the fungal cell wall
What two processes does the antifungal drug flucytosine target?
fungal DNA replication and transcription
Name the two groups of antiprotozoan drugs
antimalarial drugs and nonmalarial antiprotozoan drugs
What challenge are physicians facing with many antimalarial drugs, such as chloroquine and hydroxychloroquine?
malarial pathogen resistance
What does the antiprotozoan drug, metronidazole (Flagyl) target?
nucleic acids
How does the antihelminthic drug praziquantel work?
Paralyzes parasites such as fluke worms & tapeworms
Why are antimicrobial susceptibility tests performed?
Performed to assess if the pathogen is likely to be treatable with a particular antimicrobial drug
What is the Kirby-Bauer test?
disk diffusion test used to determine a bacterium's susceptibility to antimicrobial drugs
What is a zone of inhibition?
develops in disk diffusion antimicrobial susceptibility testing; a clear zone around the disk infused w/ a test drug
When performing the Kirby-Bauer test, how is it determined if bacteria are susceptible, resistant, or exhibit an intermediate response to an antibiotic?
o Susceptible à the measured zone of inhibition falls in the susceptible range
o Resistant à no zone of inhibition around the disk
o Intermediate à borderline response to the drug
What is minimal inhibitory concentration (MIC)?
the lowest concentration of the antimicrobial drug that inhibits the microbe's growth
Define minimum bactericidal concentration (MBC).
the minimum concentration of the drug that kills at least 99.9 percent of the bacteria present
Define antimicrobial resistance.
a situation in which a microbe, which could be a bacterium, virus, fungus, protozoan, or helminth, is not affected by a drug therapy that is intended to inhibit or eliminate the pathogen
What are superbugs?
resistance microbes that remain unaffected by the administered antimicrobial therapy and may readily increase their numbers in the patient & cause a superinfection
Define intrinsic resistance.
built-in qualities that help some bacteria naturally resist antimicrobial drugs
Define acquired resistance.
develops due to genetic mutation or when drug resistance genes are transferred/shared via horizontal gene transfer events
List three main ways that microbes evade antimicrobial drugs.
Altering the drug's target, inactivating the drug, & reducing drug concentrations inside the cell by blocking drug entry or by pumping the drug out of the cell
What do plasmids carry? How are they transferred?
Plasmids carry genes that encode drug-inactivation tools; transferred by horizontal gene transfer
What are two key factors that have accelerated drug-resistant pathogens?
Pathogen prevalence & the prolific use of diverse antimicrobial drugs
List five microbes that are on the CDC's urgent threat list.
C. difficile, drug-resistant Neisseria gonorrhoeae, drug-resistant Candida auris, carbapenem-resistant Enterobacterales (or CRE), & carbapenem-resistant Acinetobacter (CRA)